Technical Assistance Publication Series
TAP 32
Clinical Drug
Testing in
Primary Care
32
TAP
Technical Assistance Publication Series
Clinical Drug Testing in
Primary Care
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Substance Abuse and Mental Health Services Administration
Center for Substance Abuse Treatment
1 Choke Cherry Road
Rockville, MD 20857
Clinical Drug Testing in Primary Care
ii
Acknowledgments
This publication was prepared for the
Substance Abuse and Mental Health
Services Administration (SAMHSA), by
RTI International and completed by the
Knowledge Application Program (KAP),
contract numbers 270-04-7049 and 270-
09-0307, a Joint Venture of The CDM
Group, Inc., and JBS International, Inc.,
with SAMHSA, U.S. Department of Health
and Human Services (HHS). Christina
Currier served as the Contracting Ofcer’s
Representative.
Disclaimer
The views, opinions, and content of this
publication are those of the authors and do
not necessarily reect the views, opinions, or
policies of SAMHSA or HHS.
Public Domain Notice
All materials appearing in this publication
except those taken from copyrighted
sources are in the public domain and may
be reproduced or copied without permission
from SAMHSA. Citation of the source is
appreciated. However, this publication may
not be reproduced or distributed for a fee
without the specic, written authorization
of the Ofce of Communications, SAMHSA,
HHS.
Electronic Access and Copies
of Publication
This publication may be ordered from
SAMHSA’s Publications Ordering Web page
at http://store.samhsa.gov. Or, please call
SAMHSA at 1-877-SAMHSA-7 (1-877-726-
4727) (English and Español). The document
may be downloaded from the KAP Web site at
http://kap.samhsa.gov.
Recommended Citation
Substance Abuse and Mental Health Services
Administration. Clinical Drug Testing
in Primary Care. Technical Assistance
Publication (TAP) 32. HHS Publication No.
(SMA) 12-4668. Rockville, MD: Substance
Abuse and Mental Health Services
Administration, 2012.
Originating Office
Quality Improvement and Workforce
Development Branch, Division of Services
Improvement, Center for Substance Abuse
Treatment, Substance Abuse and Mental
Health Services Administration, 1 Choke
Cherry Road, Rockville, MD 20857.
HHS Publication No. (SMA) 12-4668
Printed 2012
iii
Contents
Chapter 1—Introduction .................................................1
Audience for the TAP....................................................... 1
Organization of the TAP ....................................................1
Reasons To Use Clinical Drug Testing in Primary Care ...........................2
Primary Care and Substance Use Disorders ....................................2
Development of Drug Testing ................................................3
Workplace Drug Testing ....................................................4
Drug Testing in Substance Abuse Treatment and Healthcare Settings ..............5
Differences Between Federal Workplace Drug Testing and Clinical Drug Testing......6
Caution ..................................................................6
Chapter 2—Terminology and Essential
Concepts in Drug Testing .............................................9
Drug Screening and Conrmatory Testing .....................................9
Testing Methods.......................................................... 10
Test Reliability...........................................................10
Window of Detection ......................................................11
Cutoff Concentrations .....................................................12
Cross-Reactivity ..........................................................12
Drug Test Panels .........................................................13
Test Matrix ..............................................................14
Point-of-Care Tests .......................................................14
Adulterants .............................................................14
Specimen Validity Tests ...................................................15
Clinical Drug Testing in Primary Care
Chapter 3—Preparing for Drug Testing ..................................17
Deciding Which Drugs To Screen and Test For ................................17
Choosing a Matrix ........................................................17
Specimen Availability ..................................................20
Oral Fluid ............................................................20
Sweat ...............................................................20
Blood ................................................................21
Hair.................................................................21
Breath ...............................................................22
Meconium ...........................................................23
Selecting the Initial Testing Site: Laboratory or Point-of-Care ....................23
Collection Devices .....................................................23
Laboratory Tests ......................................................24
Advantages and Disadvantages of Testing in a Laboratory ....................25
Considerations for Selecting a Laboratory ..................................25
Point-of-Care Tests ....................................................26
Advantages and Disadvantages of POCTs ..................................27
Considerations for Selecting POCT Devices ................................28
Implementing Point-of-Care Testing ......................................29
Preparing Clinical and Ofce Staffs for Testing .............................30
Preparing a Specimen Collection Site.........................................30
Chapter 4—Drug Testing in Primary Care ................................31
Uses of Drug Testing in Primary Care ........................................31
Monitoring Prescription Medication Use ................................... 32
Management of Chronic Pain With Opioids.................................32
Evaluation of Unexplained Symptoms or Unexpected Responses to Treatment ....32
Patient Safety......................................................... 33
iv
Contents
Pregnancy ............................................................33
Psychiatric Care ......................................................34
Monitoring Ofce-Based Pharmacotherapy for Opioid Use Disorders ............34
Detection of Substance Use Disorders .....................................34
Initial Assessment of a Person With a Suspected SUD........................35
Talking With Patients About Drug Testing ....................................38
Cultural Competency and Diversity .........................................39
Monitoring Patients ......................................................40
Patients With an SUD ..................................................40
Monitoring Patients Receiving Opioids for Chronic Noncancer Pain .............41
Ensuring Condentiality and 42 CFR Part 2................................... 42
Preparing for Implementing Drug Testing.....................................43
Collecting Specimens ...................................................43
Conducting POCTs ....................................................44
Interpreting Drug Test Results .............................................44
Result: Negative Specimen ..............................................45
Result: Positive Specimen ...............................................46
Result: Adulterated or Substituted Specimen ............................... 47
Result: Dilute Specimen ................................................48
Result: Invalid Urine Specimen ..........................................48
Frequency of Testing ......................................................49
Documentation and Reimbursement .........................................49
Documentation ........................................................49
Reimbursement .......................................................50
Chapter 5—Urine Drug Testing for Specic Substances ....................51
Window of Detection ......................................................51
Specimen Collection .......................................................52
v
Clinical Drug Testing in Primary Care
Adulteration, Substitution, and Dilution ......................................52
Adulteration .........................................................52
Substitution ..........................................................53
Dilute Specimens ......................................................53
Cross-Reactivity ..........................................................54
Alcohol .................................................................54
Amphetamines ...........................................................55
Barbiturates .............................................................56
Benzodiazepines.......................................................... 56
Cocaine .................................................................57
Marijuana/Cannabis ......................................................58
Opioids .................................................................58
Other Substances of Abuse ................................................. 60
PCP .................................................................60
Club Drugs ...........................................................60
LSD .................................................................61
Inhalants ............................................................61
Appendix A—Bibliography ..............................................63
Appendix B—Laboratory Initial Drug-Testing Methods ....................71
Appendix C—Laboratory Conrmatory Drug-Testing Methods..............73
Appendix D—Laboratory Specimen Validity-Testing Methods ..............75
Appendix E—Glossary ..................................................77
Appendix F—Expert Panel ..............................................79
Appendix G—Consultants and Field Reviewers ...........................81
Appendix H—Acknowledgments .........................................83
vi
Exhibits
Exhibit 1-1. U.S. Department of Health and Human Services
Federal Mandatory Workplace Guidelines Cutoff Concentrations
for Initial and Conrmatory Drug Tests in Urine .............................5
Exhibit 1-2. Comparison of Federal Workplace
Drug Testing and Clinical Drug Testing ....................................7
Exhibit 2-1. Window of Detection for Various Matrices .......................... 12
Exhibit 3-1. Advantages and Disadvantages
of Different Matrices for Drug Testing ..................................... 18
Exhibit 3-2. Comparison of Laboratory Tests and POCTs ........................24
Exhibit 3-3. Federal and State Regulations .................................... 25
Exhibit 4-1. Motivational Interviewing Resources ..............................35
Exhibit 4-2. The CAGE-AID Questions .......................................36
Exhibit 4-3. Brief Intervention Elements: FRAMES ............................. 36
Exhibit 4-4. Patient Flow Through Screening
and Referral in Primary Care ...........................................37
Exhibit 5-1. Barbiturates—Window of Detection ............................... 56
Exhibit 5-2. Benzodiazepines—Window of Detection ............................ 57
Exhibit 5-3. Opioids—Window of Detection .................................... 59
vii
1
Chapter 1—Introduction
In This Chapter
• Audience for the Tap
• Organization of the
Tap
• Reasons To Use
Clinical Drug Testing
in Primary Care
• Primary Care and
Substance Use
Disorders
• Development of Drug
Testing
• Workplace Drug
Testing
• Drug Testing in
Substance Abuse
Treatment and
Healthcare Settings
• Differences Between
Federal Workplace
and Clinical Drug
Testing
• Caution
Audience for the TAP
This Technical Assistance Publication (TAP), Clinical Drug
Testing in Primary Care, is for clinical practitioners—
physicians, nurse practitioners, and physician assistants—
who provide primary care in ofce settings and community
health centers. The publication provides information that
practitioners need when deciding whether to introduce drug
testing in their practices and gives guidance on implementing
drug testing.
The TAP does not address drug testing for law enforcement
or legal purposes, nor does it include testing for the use of
anabolic steroids or performance-enhancing substances.
This TAP describes some of the ways that drug testing can
contribute to the assessment, diagnosis, and treatment
of patients seen in primary care, the management of the
treatment of chronic pain, and the identication and
treatment of substance use disorders.
Organization of the TAP
This chapter briey describes the role of drug testing in
primary care settings and its historical roots in workplace
testing. Chapter 2 denes the terms and practices used in
drug testing. Chapter 3 presents the mechanics of testing
and describes the steps that primary care practitioners can
take to prepare themselves, their staffs, and their ofce
spaces for drug testing. Chapter 4 provides information
about implementing testing in clinical practice. Important
aspects of urine drug testing for specic drugs are presented
in Chapter 5. Appendices A–H include the bibliography;
overviews of technical information on specic tests used
for initial or screening tests, conrmatory tests, and
specimen validity tests; a glossary of terms; the members
of the expert panel, consultants, and eld reviewers; and
acknowledgments.
Clinical Drug Testing in Primary Care
2
Reasons To Use Clinical Drug
Testing in Primary Care
The term drug testing can be confusing
because it implies that the test will detect
the presence of all drugs. However, drug
tests target only specic drugs or drug
classes and can detect substances only
when they are present above predetermined
thresholds (cutoff levels). The term drug
screening can also be deceptive because it
is often used to describe all types of drug
testing. However, drug screening is usually
used in forensic drug testing to refer to the
use of immunoassay tests to distinguish
specimens that test negative for a drug and/or
metabolite from positive specimens. For the
purpose of this TAP, the term drug testing is
used.
When used appropriately, drug testing can
be an important clinical tool in patient care.
The types of clinical situations in which
clinical drug testing can be used include
pain management with opioid medications,
ofce-based opioid treatment, primary
care, psychiatry, and other situations when
healthcare providers need to determine
alcohol or other substance use in patients.
Drug testing is also used to monitor patients’
prescribed medications with addictive
potential. Patients sometimes underreport
drug use to medical professionals (Chen,
Fang, Shyu, & Lin, 2006), making some
patients’ self-reports unreliable. Drug
test results may provide more accurate
information than patient self-report.
Although drug testing can be a useful tool
for making clinical decisions, it should not be
the only tool. When combined with a patient’s
history, collateral information from a spouse
or other family member (obtained with
permission of the patient), questionnaires,
biological markers, and a practitioner’s
clinical judgment, drug testing provides
information that:
• Can affect clinical decisions on a patient’s
substance use that affects other medical
conditions.
• Can affect clinical decisions about
pharmacotherapy, especially with
controlled substances.
• Increases the safety of prescribing
medications by identifying the potential for
overdose or serious drug interactions.
• Helps clinicians assess patient use of
opioids for chronic pain management or
compliance with pharmacotherapy for
opioid maintenance treatment for opioid
use disorders.
• Helps the clinician assess the efcacy of
the treatment plan and the current level
of care for chronic pain management and
substance use disorders (SUDs).
• Prevents dangerous medication
interactions during surgery or other
medical procedures.
• Aids in screening, assessing, and
diagnosing an SUD, although drug testing
is not a denitive indication of an SUD.
• Identies women who are pregnant, or who
want to become pregnant, and are using
drugs or alcohol.
• Identies at-risk neonates.
• Monitors abstinence in a patient with a
known SUD.
• Veries, contradicts, or adds to a patient’s
self-report or family member’s report of
substance use.
• Identies a relapse to substance use.
Primary Care and Substance Use
Disorders
Practitioners can use drug testing to help
monitor patients’ use of prescribed scheduled
medications, as part of pharmacovigilance,
and to help identify patients who may need
an intervention for SUDs.
For the purpose of this TAP, substances
refers to alcohol and drugs that can be
abused. As dened by the Diagnostic and
Statistical Manual of Mental Disorders,
3
Chapter 1―Introduction
Fourth Edition, Text Revision (DSM-
IV-TR; American Psychiatric Association
[APA], 2000), a substance-related disorder
is a disorder related to the consumption of
alcohol or of a drug of abuse (APA, 2000).
Substance use disorders (SUDs) includes
both substance dependence and substance
abuse (APA, 2000). Substance dependence
refers to “a cluster of cognitive, behavioral,
and physiological symptoms indicating that
the individual continues use of the substance
despite signicant substance-related
problems. There is a pattern of repeated self-
administration that can result in tolerance,
withdrawal, and compulsive drug-taking
behavior” (APA, 2000). Substance abuse
refers to “a maladaptive pattern of substance
use manifested by recurrent and signicant
adverse consequences related to the repeated
use of substances” (APA, 2000). In this TAP,
the term substance abuse is sometimes used
to denote both substance abuse and substance
dependence as they are dened in the DSM-
IV-TR (APA, 2000).
SUDs can have serious medical complications
and serious psychosocial consequences and
can be fatal. Treatment of other medical
disorders (e.g., HIV/AIDs, pancreatitis,
hypertension, diabetes, liver disorders) may
be complicated by the presence of an SUD.
As the front line in health care, medical
practitioners are ideally situated to identify
substance use problems. The 2009 National
Survey on Drug Use and Health (Substance
Abuse and Mental Health Services
Administration [SAMHSA], 2010a) found that
23.5 million (9.3 percent) persons ages 12 or
older needed treatment for an illicit drug
1
or alcohol use problem. Of this population,
only 2.6 million (1.0 percent) persons ages
12 or older (11.2 percent of those who needed
treatment) received treatment at a specialty
facility. Thus, 20.9 million (8.3 percent) of the
population age 12 or older needed substance
abuse treatment but did not receive it in the
past year (SAMHSA, 2010a). Therefore, a
visit to a primary care practitioner may be
an excellent opportunity for such people to be
diagnosed with SUDs. Moreover, the number
of people ages 12 or older seeking help for
SUDs from a doctor in private practice
increased from 460,000 in 2005 to 672,000 in
2008 (SAMHSA, 2006; SAMHSA, 2009).
Despite the potential benets of drug testing
(such as monitoring pain medication) to
patient care, few primary care practitioners
use it. For example, a small study conducted
on the medical management of patients with
chronic pain in family practices found that
only 8 percent of physicians surveyed used
drug testing (Adams et al., 2001).
1
Includes the nonmedical use of prescription-type
pain relievers, tranquilizers, stimulants, and sedatives.
Development of Drug Testing
Drug testing performed for clinical reasons
differs substantially from workplace drug
testing programs. However, clinical drug
testing draws on the experience of Federal
Mandatory Workplace Drug Testing and,
to understand drug testing, a review of
workplace drug testing may be helpful. An
important reason for clinical practitioners
to become familiar with Federal Mandatory
Workplace Drug Testing is that the majority
of drug testing is done for workplace
purposes. For this reason, most laboratories
and many point-of-care tests (POCTs) use
the cutoff concentrations established by the
Mandatory Guidelines for Federal Workplace
Drug Testing Programs, discussed in Chapter 2.
There are three categories of drug testing:
(1) federally regulated for selected Federal
employees (including military personnel
and those in safety-sensitive positions);
(2) federally regulated for non-Federal
employees in safety-sensitive positions (i.e.,
airline and railroad personnel, commercial
truckers, school bus drivers); and (3)
nonregulated for non-Federal employees.
Commercial truck drivers, railroad employees
and airline personnel make up the largest
group of individuals being drug tested.
The purpose of both Federal (always
regulated) and non-Federal (may be
nonregulated) workplace drug testing is to
ensure safety in the workplace by preventing
Clinical Drug Testing in Primary Care
4
the hiring of individuals who use illicit drugs
and identifying employees who use illicit
drugs.
Workplace Drug Testing
Drug-testing methods have been available
for approximately 50 years (Reynolds, 2005).
Because of drug use in the U.S. military, by
1984, the military established standards for
laboratories and testing methods and created
the rst system for processing large numbers
of drug tests under strict forensic conditions
that could be defended in a court of law.
In 1986, an Executive Order initiated the
Federal Drug-Free Workplace Program that
dened responsibilities for establishing a
plan to achieve drug-free workplaces. In
1987, Public Law 100-71 outlined provisions
for drug testing programs in the Federal
sector. In 1988, Federal mandatory guidelines
set scientic and technical standards for
testing Federal employees. In 1989, the U.S.
Department of Transportation (DOT) issued
regulations requiring the testing of nearly 7
million private-sector transportation workers
in industries regulated by DOT.
The Federal mandatory guidelines included
procedures, regulations, and certication
requirements for laboratories; outlined the
drugs for which testing was to be performed;
set cutoff concentrations; and stated reporting
requirements that included mandatory medical
reviews by a specially trained physician
Medical Review Ofcer (MRO). Because a
positive result does not automatically identify
an employee or job applicant as a person
who uses illicit drugs, the MRO interviews
the donor to determine whether there is an
alternative medical explanation for the drug
found in the specimen. The Federal mandatory
guidelines recommended that the initial
screening test identify the presence of the
following commonly abused drugs or their
metabolites (SAMHSA, 2008):
• Amphetamines (amphetamine,
methamphetamine)
• Cocaine metabolites
• Marijuana metabolites
• Opiate metabolites (codeine, morphine)
• Phencyclidine (PCP)
These substances are generally called the
“Federal 5,” but over the years they have also
been called the “NIDA 5” and “SAMHSA 5.”
The Federal mandatory guidelines have been
updated and revised over the years to reect
technological and process changes (Exhibit
1-1). The guidelines, last updated in 2008
(effective May 1, 2010), are available at http://
dwp.samhsa.gov/DrugTesting/Level_1_Pages/
mandatory_guidelines5_1_10.html.
Revisions for testing of other matrixes (e.g.,
hair, oral uid, sweat) and the use of POCTs
were proposed in 2004 (SAMHSA, 2008), but
have not been nalized.
Although Federal agencies are required
to have drug-free workplace programs for
their employees, private-sector employers
that do not fall under Federal regulations
can establish their own drug-free workplace
programs and establish their own
regulations, testing matrices, and testing
methods. Non-Federal employees can be
tested for a broader range of drugs than the
federally mandated drugs. Many States have
laws and regulations that affect when, where,
and how employers can implement drug-free
workplace programs (search in http://www.
dol.gov).
Laboratories are accredited by the National
Laboratory Certication Program (NLCP)
to meet the minimum requirements of the
Federal mandatory guidelines. This program
resides in SAMHSA in the Department of
Health and Human Services (HHS).
Chapter 1―Introduction
Exhibit 1-1. U.S. Department of Health and Human Services Federal Mandatory Workplace
Guidelines Cutoff Concentrations for Initial and Confirmatory Drug Tests in Urine
Initial Test Analyte
Federal Cutoff
Concentrations (ng/mL)
Marijuana metabolites 50
Cocaine metabolites 150
Opiate metabolites (codeine/morphine
1
) 2,000
6-Acetylmorphine (6-AM) 10
Amphetamines
2
(Amphetamine /methamphetamine) 500
Phencyclidine (PCP) 25
Methylenedioxymethamphetamine (MDMA) 500
Confirmatory Test Analyte
Federal Cutoff
Concentrations (ng/mL)
Amphetamine 250
Methamphetamine
3
250
MDMA 250
Methylenedioxyamphetamine (MDA) 250
Methylenedioxyethylamphetamine (MDEA) 250
Cannabinoid metabolite (delta-9-tetrahydrocannabinol-9-carboxylic acid) 15
Cocaine metabolite (benzoylecgonine) 100
Codeine 2,000
Morphine 2000
6-Acetylmorphine (6-AM) 10
PCP 25
Source: SAMHSA (2008).
1
Morphine is the target analyte for codeine/morphine testing.
2
Methamphetamine is the target analyte for amphetamine/methamphetamine testing.
3
To be reported positive for methamphetamine, a specimen must also contain amphetamine at a concentration equal to, or greater
than, 100 ng/mL.
Drug Testing in Substance Abuse
Treatment and Healthcare Settings
Substance abuse treatment programs
use drug testing extensively. Drug
testing for patient monitoring in SUD
treatment programs began considerably
before workplace drug testing and has
become an integral part of many drug
treatment programs for patient evaluation
and monitoring. By 1970, the Federal
Government implemented specic mandatory
testing requirements for treatment programs
that were licensed by the U.S. Food and
Drug Administration to dispense methadone
or that received Federal funds. During the
1970s, Federal agencies developed a program
to monitor laboratories performing drug
testing for drug treatment programs under
Federal mandates.
Drug testing in SUD treatment is:
• Part of the initial assessment of a patient
being evaluated for a diagnosis of an SUD;
• A screen to prevent potential adverse
effects of pharmacotherapy (e.g., opioid
screen prior to starting naltrexone);
• A component of the treatment plan for an
SUD;
• A way to monitor the patient’s use
of illicit substances or adherence to
pharmacotherapy treatment for SUDs; and
• A way to assess the efcacy of the
treatment plan (i.e., level of care).
5
Clinical Drug Testing in Primary Care
6
Drug testing can also be used to document
abstinence for legal matters, disability
determinations, custody disputes, or
reinstatement in certain professions (e.g.,
lawyers, healthcare providers, airline pilots).
Drug testing is also useful in healthcare
settings:
• For determining or refuting perinatal
maternal drug use;
• As an adjunct to psychiatric care and
counseling;
• For monitoring medication compliance
during pain treatment with opioids;
• For monitoring other medications that
could be abused or diverted; and
• To detect drug use or abuse where it may
have a negative impact on patient care in
other medical specialties.
See Chapter 4 for more information about the
use of drug testing in clinical situations.
Differences Between Federal
Workplace Drug Testing and
Clinical Drug Testing
Important distinctions exist between drug
testing in Federal workplace settings and
drug testing in clinical settings (Exhibit 1-2).
Despite the differences, Federal workplace
drug-testing guidelines and cutoff
concentrations continue to inuence clinical
drug testing. For example, many laboratories
and POCT devices test either for the federally
mandated drugs or for the same drugs, but
using modied cutoff concentrations as the
default drug-testing panel. These panels are
not suitable for clinical drug testing because
these panels do not detect some of the most
commonly prescribed pain medications, such
as synthetic opioids (e.g., hydrocodone) and
anxiolytics (e.g., benzodiazepines, such as
alprazolam), or other drugs of abuse. Initial
screening test cutoffs may not be low enough
for clinical practice in some instances (e.g.,
cannabinoids, opiates, amphetamines).
Caution
Trends in drug use and abuse change over
time and can necessitate a change in drug
testing panels. The technology for drug
testing evolves quickly, new drug-testing
devices become available, and old tests are
rened. Although this TAP presents current
information, readers are encouraged to
continue to consult recent sources. Wherever
possible, the TAP refers readers to resources
that provide up-to-date information.
Chapter 1―Introduction
• Policies minimize mistaken identity of
specimens and specimen adulteration.
For example, in criminal cases,
chain-of-custody policies require
identification of all persons handling
specimen packages. In administrative
cases (e.g., workplace testing), specimen
packages may be handled without
individual identification. Only those persons
handling the specimen itself need to be
identified.
• Pain management laboratories may have
specimen validity testing pr
otocols that involve
creatinine with reflexive specific gravity, pH,
and/or oxidants in place.
Exhibit 1-2. Comparison of Federal Workplace Drug Testing and Clinical Drug Testing
Component Federal Workplace Testing Clinical Testing
Specimen
• Urine • Primarily urine, some oral fluid tests
Collection
Procedures
• Federal regulations stipulate specimen
collection procedures.
• Practitioners and clinical staff (hospital or clinical
laboratory) follow procedures for properly
identifying and tracking specimens.
• In general, rigorous protocols are not used.
Chain of custody usually is not required;
however, laboratories under College of American
Pathologists accreditation and/or State licensure
should have specimen collection, handling, and
storage protocols in place.
Specimen
Validity Testing
• Extensive testing verifies that specimen
substitution or adulteration has not
occurred.
• In general, laboratories do not conduct the
same validity testing as is required for Federal
workplace testing.
• Validation often is not required with clinical use
of POCT.
• Some laboratories record the temperature of
the specimen and test for creatinine and specific
gravity of urine specimens.
Confirmatory
Methods
• Gas chromatography/mass spectrometry
(GC/MS)
• GC/MS, liquid chromatography/mass
spectrometry (LC/MS), liquid chromatography/
mass spectrometry/mass spectrometry LC/MS/
MS.
Testing for
Predetermined
Substances
• Testing is for the federally mandated drugs. • No set drug testing panel.
• Drugs tested vary by laboratory and within
laboratories.
• Clinicians may specify which drugs are tested for
and usually select panels (menus) that test for
more than the federally mandated drugs. Various
panels exist (e.g., pain).
Cutoff
Concentrations
• Cutoff concentrations have been
established for each drug.
• A test detecting a concentration at or
above the cutoff is considered to be a
positive result; a test detecting nothing,
or a concentration below the cutoff, is
considered to be a negative result.
• Cutoff concentrations vary.
• In some circumstances, test results below the
cutoff concentration may be clinically significant.
• Urine and oral fluid drug concentrations are
usually not well correlated with impairment
or intoxication, but may be consistent with
observed effects.
Laboratory
Certification
• Testing must be conducted at an HHS,
SAMHSA-certified laboratory.
• Laboratories do not need HHS certification.
However, clinical laboratories in the United
States and its territories must be registered with
Clinical Laboratory Improvement Amendments
(CLIA) and comply with all State and local
regulations concerning specimen collection,
clinical laboratory testing, and reporting.
• POCT using kits calibrated and validated
by manufacturers does not require CLIA
certification.
Medical Review
• A physician trained as an MRO must
interpret and report results.
• MRO review is not required.
7
9
Chapter 2—Terminology and Essential
Concepts in Drug Testing
In This Chapter
• Drug Screening and
Conrmatory Testing
• Testing Methods
• Test Reliability
• Window of Detection
• Cutoff Concentrations
• Cross-Reactivity
• Drug Test Panels
• Test Matrix
• Point-of-Care Tests
• Adulterants
• Specimen Validity
Tests
Drug Screening and Confirmatory Testing
Traditionally, drug testing usually, but not always, involves
a two-step process: an initial drug screen that identies
potentially or presumptively positive and negative specimens,
followed by a conrmatory test of any screened positive
assays.
Screening tests (the initial tests) indicate the presence
or absence of a substance or its metabolite, but also can
indicate the presence of a cross-reacting, chemically similar
substance. These are qualitative analyses—the drug (or drug
metabolite) is either present or absent. The tests generally
do not measure the quantity of the drug or alcohol or its
metabolite present in the specimen (a quantitative analysis).
Screening tests can be done in a laboratory or onsite
(point-of-care test [POCT]) and usually use an immunoassay
technique. Laboratory immunoassay screening tests are
inexpensive, are easily automated, and produce results
quickly. Screening POCT immunoassay testing devices are
available for urine and oral uids (saliva). Most screening
tests use antigen–antibody interactions (using enzymes,
microparticles, or uorescent compounds as markers) to
compare the specimen with a calibrated quantity of the
substance being tested for (Center for Substance Abuse
Treatment, 2006b).
Conrmatory tests either verify or refute the result of the
screening assay. With recent improvements in conrmation
technology, some laboratories may bypass screening tests
and submit all specimens for analysis by conrmatory
tests. It is the second analytical procedure performed on
a different aliquot, or on part, of the original specimen to
identify and quantify the presence of a specic drug or drug
metabolite (Substance Abuse and Mental Health Services
Administration [SAMHSA], 2008). Conrmatory tests use
a more specic, and usually more
sensitive, method than do
screening tests and are usually performed in a laboratory.
Conrmatory tests usually:
• Provide quantitative concentrations (e.g., ng/mL) of specic
substances or their metabolites in the specimen.
• Have high specicity and sensitivity.
Clinical Drug Testing in Primary Care
10
• Require a trained technician to perform
the test and interpret the results.
• Can identify specic drugs within drug
classes.
In clinical situations, conrmation is not
always necessary. Clinical correlation is
appropriate. For example, if the patient
or a family member afrms that drug use
occurred, a conrmation drug test is not
usually needed.
A POCT, performed where the specimen is
collected, is a screening test. A conrmatory
drug test is usually more technically complex
and provides denitive information about
the quantitative concentrations (e.g., ng/mL)
of specic drugs or their metabolites in the
specimen tested. However, the term drug
screening or testing is misleading in that it
implies that all drugs will be identied by
tests, whereas the drug or drug metabolites
detected by a test depend on the testing
method and the cutoff concentration.
In Federal workplace testing, all positive
initial screening test results must be followed
by a conrmatory test (SAMHSA, 2008).
In clinical settings, however, conrmatory
testing is at the practitioner’s discretion.
Laboratories do not automatically perform
conrmatory tests. When a patient’s
screening test (either a POCT or laboratory
test) yields unexpected results (positive
when in substance use disorder (SUD)
treatment, or negative if in pain management
treatment), the practitioner decides whether
to request a conrmatory test. In addition,
a conrmatory test may not be needed;
patients may admit to drug use or not taking
scheduled medications when told of the
drug test results, negating the necessity
of a conrmatory test. However, if the
patient disputes the unexpected ndings, a
conrmatory test should be done. Chapter 4
provides information that can be helpful in
deciding whether to request a conrmatory
test.
Testing Methods
Conventional scientic techniques are
used to test specimens for drugs or drug
metabolites. Most commonly, immunoassay
testing technology is used to perform the
initial screening test (Meeker, Mount, &
Ross, 2003). Appendix B, Laboratory Initial
Drug-Testing Methods, briey describes these
methods.
The most common technologies used to
perform the conrmatory test are gas
chromatography/mass spectrometry, liquid
chromatography/mass spectrometry, and
various forms of tandem mass spectrometry.
Information about these methods and other
conrmatory testing methods are in Appendix
C, Laboratory Conrmatory Drug-Testing
Methods. Other testing methods are used to
detect adulteration or substitution. Appendix
D, Laboratory Specimen Validity-Testing
Methods, provides a short explanation of
methods for specimen validity testing.
Test Reliability
Both POCTs and laboratory tests are
evaluated for reliability. Two measures
of test reliability are sensitivity and
specicity, which are statistical measures
of the performance of a test. The sensitivity
indicates the proportion of positive results
that a testing method or device correctly
identies. For drug testing, it is the test’s
ability to reliably detect the presence of a
drug or metabolite at or above the designated
cutoff concentration (the true-positive
rate). Specicity is the test’s ability to
exclude substances other than the analyte
of interest or its ability not to detect the
analyte of interest when it is below the cutoff
concentration (the true-negative rate). It
indicates the proportion of negative results
that a testing method or device correctly
identies.
11
Chapter 2—Terminology and Essential Concepts in Drug Testing
Tests are designed to detect whether a
specimen is positive or negative for the
substance. Four results are possible:
• True positive: The test correctly detects the
presence of the drug or metabolites.
• False positive: The test incorrectly detects
the presence of the drug when none is
present.
• True negative: The test correctly conrms
the absence of the drug or metabolites.
• False negative: The test fails to detect the
presence of the drug or metabolites.
Conrmatory tests must have high
specicity. Generally, screening tests have
relatively low specicity. Screening tests are
manufactured to be as sensitive as possible,
while minimizing the possibility of a false-
positive result (Dolan, Rouen, & Kimber,
2004). Notable exceptions from common
manufacturers of laboratory-based or point-
of-care immunoassay kits are cannabinoids,
cocaine metabolite, oxycodone/oxymorphone,
methadone, and methadone metabolite
(EDDP, or 2-ethylidine-1,5-dimethyl-3,3-
diphenylpyrrolidine). Other examples may
exist. With the exceptions noted previously,
they cannot reliably exclude substances other
than the substance of interest (the analyte),
and they cannot reliably discriminate among
drugs of the same class. For example, a low-
specicity test may reliably detect morphine,
but be unable to determine whether the drug
used was heroin, codeine, or morphine.
Generally, the cutoff level for initial screening
tests is set to identify 95–98 percent of
true-negative results, and 100 percent of
true-positive results. Conrmatory test
cutoff concentrations are set to ensure that
more than 95 percent of all specimens with
screened positive results are conrmed as
true positives (Reynolds, 2005). However,
conrmation rates are highly dependent upon
the analyte. For cannabinoids and cocaine
metabolite, the conrmatory rate usually
exceeds 99 percent. The clinically important
point is that false positives are rare for
cocaine metabolite or cannabinoids.
Window of Detection
The window of detection, also called the
detection time, is the length of time the
substances or their metabolites can be
detected in a biological matrix. It part, it
depends on:
• Chemical properties of the substances for
which the test is being performed;
• Individual metabolism rates and excretion
routes;
• Route of administration, frequency of use,
and amount of the substance ingested;
• Sensitivity and specicity of the test;
• Selected cutoff concentration;
• The individual’s health, diet, weight,
gender, uid intake, and pharmacogenomic
prole; and
• The biological specimen tested.
All biological matrices may show the presence
of both parent drugs and their metabolites
(Warner, 2003). Drug metabolites usually
remain in the body longer than do the parent
drugs. Blood and oral uid are better suited
for detecting the parent drug; urine is most
likely to contain the drug’s metabolites.
Exhibit 2-1 provides a comparison of
detection periods used for various matrices.
Many factors inuence the window of
detection for a substance. Factors include,
but are not limited to, the frequency of drug
use (chronic or acute), the amount taken, the
rate at which the substance is metabolized
(including pharmacogenomic abnormalities,
such as mutations of CYP2D6 and other
drug-metabolizing enzymes [White & Black,
2007]), the cutoff concentration of the test,
the patient’s physical condition and, in many
cases, the amount of body fat.
Exhibit 2-1. Window of Detection for Various Matrices
Matrix Time*
Breath
Blood
Oral Fluid
Urine
Sweat
†
Hair‡
Meconium
Minutes Hours Days Weeks Months Years
Clinical Drug Testing in Primary Care
12
*Very broad estimates that also depend on the substance, the amount and frequency of the substance taken, and other factors
previously listed.
†As long as the patch is worn, usually 7 days.
‡7–10 days after use to the time passed to grow the length of hair, but may be limited to 6 months hair growth. However, most
laboratories analyze the amount of hair equivalent to 3 months of growth.
Sources: Adapted from Cone (1997); Dasgupta (2008).
Cutoff Concentrations
The administrative cutoff threshold
drug test is the point of measurement at or
above which a result is considered positive
and below which a result is considered
negative. This level is established on the
basis of the reliability and accuracy of
the test and its ability to detect a drug or
metabolite for a reasonable period after drug
use (see Test Reliability).
(or ) of a
Before the establishment of the Federal
mandatory guidelines, cutoff concentrations
for screening tests were determined by the
manufacturer of the test or the laboratory.
Because the majority of drug testing is done
for workplace purposes, most laboratories
and many POCTs use the Federal mandatory
guidelines for workplace testing cutoff
concentrations. However, Federal cutoff
concentrations are not appropriate for
clinical use. Practitioners need to know the
cutoff concentrations used in the POCTs,
or by the laboratory testing their patients’
specimens, and should understand which
analyte and at what cutoff the test is
designed to detect.
Detection thresholds for Federal, employer,
and forensic drug testing panels are set high
enough to detect concentrations suggesting
drug abuse, but they do not always detect
therapeutic concentrations of medications.
For example, the threshold for opiates in
federally mandated workplace urine drug
screening is 2000 ng/mL. The usual screening
threshold for opiates in clinical monitoring
is much lower, at 300 ng/mL for morphine,
hydrocodone, and codeine (Christo et al.,
2011) to detect appropriate use of opioid pain
medication.
For laboratory tests, practitioners can
request lower cutoff concentrations than
are commonly used in workplace testing.
However, in some cases, the error rate
increases as the cutoff concentration
decreases.
Cross-Reactivity
Cross-reactivity occurs when a test cannot
distinguish between the substances being
tested for and substances that are chemically
similar. This is a very important concept
when interpreting test results.
13
Chapter 2—Terminology and Essential Concepts in Drug Testing
Drug class-specic immunoassay tests
compare the structural similarity of a
drug or its metabolites with specially
engineered antibodies. The ability to detect
the presence of a specic drug varies with
different immunoassay tests, depending
on the cross-reactivity of the drug with an
antibody. For example, a test for opioids may
be very sensitive to natural opioids, such
as morphine, but may not cross-react with
synthetic or semisynthetic opioids, such as
oxycodone.
Substances other than the drug to be detected
may also cross-react with the antibody
and produce a false-positive result. Some
over-the-counter (OTC) decongestants (e.g.,
pseudoephedrine) register a positive drug
test result for amphetamine. Phentermine,
an anorectic agent, commonly yields a
false-positive initial amphetamines test.
Dextromethorphan can produce false-positive
results for phencyclidine (PCP) in some assays.
Cross-reactivity can be benecial in clinical
testing. As an example, a urine test that
is specic for morphine will detect only
morphine in a patient’s urine. The morphine-
specic test will miss opioids, such as
hydrocodone and hydromorphone. A urine
drug test or panel that is reactive to a wide
variety of opioids would be a better choice for
a clinician when looking for opioid use by a
patient. Conversely, the lack of sensitivity to
the common semisynthetic opioid, oxycodone,
is detrimental to patient care when a
clinician is reviewing the results of a “urine
drug screen” and sees “opiates negative”
when oxycodone abuse is suspected. Thus,
cross-reactivity can be a double-edged sword
in clinical practice.
To avoid false-positive results caused by
cross-reactivity, practitioners should be
familiar with the potential for cross-reactivity
and ask patients about prescription and OTC
medication use.
Drug-testing accuracy continues to improve.
For example, newer drug tests may correct
for interactions that have been formerly
associated with false-positive results.
Practitioners can nd some of this
information in the instructions in the POCT
packaging material, or they can talk with
laboratory personnel to know exactly what a
laboratory’s tests will and will not detect.
Drug Test Panels
A drug test panel is a list (or menu) of drugs
or drug classes that can be tested for in a
specimen. These can be ordered to identify
drugs of abuse or in pain management.
No single drug panel is suitable for all
clinical uses; many testing options exist
that can be adapted to clinical needs. These
panels are designed to monitor adherence
to pain treatment plans, to detect use
of nonprescribed pain medications, and
to screen for use of illicit drugs. Clinical
practitioners can order more comprehensive
drug test panels to identify drugs or classes of
drugs that go beyond the federally mandated
drugs for testing. Which drugs are included
in the testing menu vary greatly between
and within laboratories; laboratories differ
in the drugs or metabolites included in their
comprehensive panel and have more than
one type of panel. Therefore, practitioners
should contact their laboratory to determine
the capabilities and usual practices of the
laboratory. It is just as important for a
clinical practitioner to know what a “urine
drug screen” will not detect as it is to know
what it will detect. Some laboratories have
a comprehensive pain management panel
for people prescribed opioids for pain (Cone,
Caplan, Black, Robert, & Moser, 2008).
Panels can be customized for individual
practices or patients, but using existing
test panels from the laboratory is generally
less expensive for patients and less time-
consuming for practitioners than ordering
tests for many individual substances.
However, these panels vary by laboratory
and are not standardized. However, it
should be noted that laboratories may default
to the federally mandated drug tests if a
practitioner does not order a different test
panel.
Clinical Drug Testing in Primary Care
14
Panels are available in various congurations.
The more drugs on a panel, the more
expensive the test. Substances typically on
these panels include, but are not limited to:
• Amphetamine, methamphetamine.
• Barbiturates (amobarbital, butabarbital,
butalbital, pentobarbital, phenobarbital,
secobarbital).
• Benzodiazepines (alprazolam,
chlordiazepoxide, clonazepam, clorazepate,
diazepam, urazepam, lorazepam,
oxazepam, temazepam).
• Illicit drugs (cocaine,
methylenedioxyamphetamine [MDA],
methylenedioxymethamphetamine [MDMA],
methylenedioxyethylamphetamine [MDEA],
marijuana).
• Opiates/opioids (codeine, dihydrocodeine,
fentanyl, hydrocodone, hydromorphone,
meperedine, methadone, morphine,
oxycodone, oxymorphone, propoxyphene).
The practitioner should consult with the
laboratory when determining the preferred
test panels.
The test menu for POCTs differs per
the manufacturer and the device. Most
POCTs screen for drugs included in the
federally mandated test panel and other
drugs or metabolites. Different devices and
manufacturers offer various congurations of
drugs tested for in devices.
Test Matrix
A test matrix is the biological specimen used
for testing for the presence of drugs or drug
metabolites. Almost any biological specimen
can be tested for drugs or metabolites, but
the more common matrices include breath
(alcohol), blood (plasma, serum), urine, sweat,
oral uid, hair, and meconium. Depending
on its biological properties, each matrix
can provide different information about a
patient’s drug use. For example, the ratio
of parent drug to metabolite in each matrix
can be decidedly different, and each matrix
has a different window of detection. Urine
is the most widely used test matrix (Watson
et al., 2006). Detailed information about test
matrices is in Chapter 3.
Point-of-Care Tests
A POCT is conducted where the specimen is
collected, such as in the practitioner’s ofce.
POCTs use well-established immunoassay
technologies for drug detection (Watson et al.,
2006).
POCTs:
• Reveal results quickly;
• Are relatively inexpensive ($5–$20,
depending on the POCT, the drugs or drug
metabolites tested for, and the number of
tests purchased);
• Are relatively simple to perform; and
• Are usually limited to indicating only
positive or negative results (qualitative,
not quantitative).
When reading the test results, it is important
to know that how quickly the test becomes
positive or the depth of the color do not
indicate quantitative results.
A comparison of POCTs and laboratory tests
is in Chapter 3.
Adulterants
An adulterant is a substance patients can
add to a specimen to mask the presence of
a drug or drug metabolite in the specimen,
creating an incorrect result to hide their drug
use. Methods to detect adulterants exist, and
most laboratories and some POCTs can detect
common adulterants. No one adulterant
(with the exception of strong acids, bases,
oxidizers, and reducing agents) can mask
the presence of all drugs. The effectiveness
of an adulterant depends on the amount of
the adulterant and the concentration of the
drug in the specimen. A specimen validity
15
Chapter 2—Terminology and Essential Concepts in Drug Testing
test can detect many adulterants. Numerous
adulterants are available, especially for urine
(see Chapter 5).
Specimen Validity Tests
Specimen validity tests determine whether a
urine specimen has been diluted, adulterated,
or substituted to obtain a negative result.
A specimen validity test can compare urine
specimen characteristics with acceptable
density and composition ranges for human
urine, detect many adulterants (e.g.,
oxidizing compounds), or test for a specic
compound (e.g., nitrite, chromium VI) at
concentrations indicative of adulteration.
Many laboratories perform creatinine and
pH analyses of all specimens submitted for
drug testing. An adulteration panel can be
ordered that determines the characteristics
of the urine sample (e.g., creatinine level
with reexive specic gravity when a low
creatinine is encountered) and checks for
the presence of common adulterants. POCT
devices are available that test for specimen
validity, as well.
Although validity testing is not required in
clinical settings, it is sometimes advisable if
the patient denies drug use. For example, a
physician treating a patient for an SUD may
want to request validity testing if the patient
exhibits signs of relapse, but has negative
test results. Point-of-care validity tests are
available, and some POCT devices also test
for validity at the same time they test for the
drug analyte.
Additional information on validity follows:
• The pH for normal urine uctuates
throughout the day, but usually ranges
between approximately 4.5 and 9.0.
Specimens outside this range are usually
reported by the laboratory as invalid.
Specimen adulteration should be suspected
if the pH level is less than 3.0 or greater
than 11.0.
• Creatinine is a normal constituent in urine
at concentrations greater than or equal to
20 mg/dL. If the creatinine is less than 20
mg/dL, the specimen is tested for specic
gravity.
• Specic gravity of urine is a measure of
the concentration of particles in the urine.
Only specimens whose creatinine is less
than 20 mg/dL need to be reexively
tested for specic gravity, although
specic gravity may be an integral part of
a POCT device’s specic validity testing
panel. Specimens with a low creatinine
and an abnormal specic gravity may be
reported as dilute, invalid, or substituted,
depending on the laboratory’s reporting
policies (SAMHSA, 2008).
If the laboratory nds the specimen is
dilute, it will report the specimen as dilute.
However, the laboratory will also report the
positive or negative test results. Depending
on the degree of dilution, an analyte may still
be detected.
Appendix D provides more information on
laboratory specimen validity tests.
17
Chapter 3—Preparing for Drug Testing
In This Chapter
• Deciding Which Drugs
To Screen and Test
For
• Choosing a Matrix
• Selecting the
Initial Testing
Site: Laboratory or
Point-of-Care
• Preparing a Specimen
Collection Site
Deciding Which Drugs To Screen and Test For
When using drug tests to screen a patient for substance use
disorders, the practitioner should test for a broad range of
drugs. Decisions about which substances to screen for can be
based on:
• The patient, including history, physical examination, and
laboratory ndings;
• The substance suspected of being used;
• The substances used locally (the Substance Abuse and
Mental Health Services Administration’s [SAMHSA’s]
Drug Abuse Warning Network compiles prevalence data
on drug-related emergency department visits and deaths;
information is available at http://www.samhsa.gov/data/
DAWN.aspx);
• The substances commonly abused in the practitioners’
patient population; and
• Substances that may present high risk for additive or
synergistic interactions with prescribed medication (e.g.,
benzodiazepines, alcohol).
Choosing a Matrix
Practitioners can choose among several matrices for drug
and alcohol testing for adults: urine, oral uid, sweat, blood,
hair, and breath (alcohol only). Neonates can be tested using
meconium. Urine is the most commonly used matrix for drug
testing and has been the most rigorously evaluated (Watson
et al., 2006); it is discussed at length in Chapter 5. Exhibit
3-1 provides a brief comparison of the advantages and
disadvantages of the seven matrices.
Clinical Drug Testing in Primary Care
Exhibit 3-1. Advantages and Disadvantages of Different Matrices for Drug Testing
Matrix Advantages Disadvantages
Urine
• Available in sufficient quantities
• Higher concentrations of parent drugs
and/or metabolites than in blood
• Availability of point-of-care tests (POCTs)
• Well-researched testing techniques
• Short to intermediate window of detection
• Easy to adulterate or substitute
• May require observed collection
• Some individuals experience “shy bladder”
syndrome and cannot produce a specimen
Oral Fluid • Noninvasive specimen collection
• Easy to collect
• Reduced risk of adulteration
• Directly observed specimen collection
• Parent drug rather than metabolite can be
the target of the assay
• Able to detect same-day use, in some
cases
• Availability of POCTs
• Detect residual drug in the mouth
• Limited specimen volume
• Possibility of contamination from residual
drug in mouth that cannot be correlated
with blood concentrations
• Short window of detection
• Requires supervision of patient for 10−30
minutes before sampling
• Salivation reduced by stimulant use
• Need for elution solvent to efficiently
remove drugs adsorbed to collection
device
• Cannabinoids in oral fluid have been shown
to arise from contamination of the oral
cavity rather than excretion in saliva from
blood
Sweat • Detects recent use (fewer than 24 hours
with a sweat swipe) or allows for cumulative
testing with the sweat patch (worn for up to
7–14 days)
• Noninvasive specimen collection
• Difficult to adulterate
• Requires little training to collect specimen
• May be an economical alternative to urine
• Few facilities and limited expertise for
testing
• Risk of accidental or deliberate removal of
the sweat patch collection device
• Unknown effects of variable sweat excretion
among individuals
• Only a single sweat collection patch
available so multiple analyses cannot be
done if needed (i.e., more than one positive
initial test)
• May be affected by external contaminants
• Requires two visits, one for patch
placement and one for patch removal
Blood • Generally detects recent use
• Established laboratory test method
• Expensive, except to detect ethanol
• Limited window of detection
• Invasive specimen collection (venipuncture)
• Risk of infection
• Requires training to collect specimen
• May not be an option for individual with
poor venous access
18
Chapter 3―Preparing for Drug Testing
• Cannot detect use within the previous
7–10 days
• Difficult to detect low-level use (e.g.,
single-use episode)
Exhibit 3-1. Advantages and Disadvantages of Different Matrices for Drug Testing, continued
Matrix Advantages Disadvantages
Hair • Longest window of detection
• May be able to detect changes in drug use
over time (from 7–10 days after drug use
to 3 months, depending on length of hair
tested)
• Directly observed specimen collection
• Noninvasive specimen collection
• Four tests will cover 1 year
• Easy storage and transport
• Difficult to adulterate or substitute
• Readily available sample, depending on
length of hair tested
• Difficult to interpret results
• Costly and time consuming to prepare
specimen for testing
• Few laboratories available to perform
testing
• No POCTs currently available
• May be biased with hair color (dark
hair contains more of some basic drugs
[cocaine, methamphetamine, opioids] due
to enhanced binding to melanin in hair)
• Possibility of environmental contamination
• Specimen can be removed by shaving
Breath • Well-established method for alcohol testing
• Readily available
• Used only for alcohol and other volatiles
• Short window of detection
• May be difficult to obtain adequate sample,
especially with patients who are very
intoxicated or uncooperative
• Uncommon in clinical setting
Meconium • Can detect maternal drug abuse and fetal
or infant exposure
• Wide window of drug detection (third
trimester of gestation)
• Noninvasive collection from diaper
• Generally, adequate specimen amount
• Narrow collection window that can be
missed, especially in babies with low birth
weight
• Testing not available in all laboratories
• Requires extra steps (weighing and
extraction)
• Confirmation assays more difficult than for
urine
Sources: Center for Substance Abuse Treatment (2006a); Dolan, Rouen, & Kimber (2004); Kwong & Ryan (1997); Warner (2003).
Once ingested, drugs of abuse are rapidly
distributed via the blood to all parts of the
body. Abused drugs are generally lipid
soluble and are mainly metabolized by the
liver to more water-soluble metabolites.
These metabolites are removed from blood by
the kidneys and excreted in urine. Because
many drugs are cleared from the blood
rapidly, testing of blood or its components
(serum) has short periods of detection,
as does breath for testing for alcohol
consumption and oral uids because the
drug passes quickly into, and is eliminated
from, breath and oral uids. Depending on
the drug itself and previously listed factors
that affect metabolism, urine usually has a
window of detection that is slightly longer
than oral uid. Urine detection times vary
from less than 1 day after ingestion to several
weeks. Hair has a longer window of detection,
but is best suited for detection of heavy drug
use. The cells that generate hair absorb the
metabolites that are circulating in the blood
at the time the hair is produced; therefore,
hair has the longest window of detection,
depending on the length of the hair. It is
notable that drugs may be incorporated
into hair from external sources, such as
mechanical contact between the hair and
the drug. In utero drug exposure also can be
monitored with maternal and neonatal urine
and/or hair testing.
19
Clinical Drug Testing in Primary Care
20
Specimen Availability
Some specimens are more easily collected
than others. Collection of blood samples
requires trained personnel to perform
venipuncture and is more invasive than
collection of urine, oral uid, or hair
specimens. Collections of oral uid and hair
are less intrusive than urine collection.
Oral Fluid
During the past decade, the use of oral uid
for drug testing has been validated by a
large body of scientic literature (Bosker &
Huestis, 2009; Cone & Huestis, 2007). The
parent drug is usually found in oral uids,
although the metabolite(s) may be present
and quite useful. The parent drug is generally
found in higher concentrations in oral uids
than are drug metabolites. Compared with
urine specimens, oral uid specimens present
fewer opportunities for adulteration or
substitution (Dams, Choo, Lambert, Jones, &
Huestis, 2007). Use of commercial adulterants
or mouthwashes were not found to interfere
with the immunoassay (Bosker & Huestis,
2009), or they did not affect test results if
the products are used more than 30 minutes
before specimen collection (Drummer, 2006;
Niedbala, Kardos, & Fries, et al., 2001;
Niedbala, Kardos, Fritch, Cannon & Davis,
2001). The window of detection for oral
uid is narrower than it is for urine, and
drug concentrations are generally lower
(Warner, 2003). In general, drug testing
of oral uids detects drug use during the
previous 24–48 hours, regardless of the route
of administration (Cone, 2006), although the
selection of cutoffs plays an important role in
the length of the detection window.
Oral uid collection devices vary, but the
most common version is a swab or absorbent
pad on a stick that is placed between the
lower cheek and gums to collect uid and
is left in place for a few minutes. It is then
inserted into a vial containing a buffer
solution for shipment to the laboratory.
POCTs are also available for oral uid
testing.
On occasion, dry mouth syndrome can slow
oral uid collection, often requiring several
minutes to collect an adequate sample
(Drummer, 2006). Some medications and
illegal drugs cause a dry mouth, and some
oral uid collection devices assist collection
by stimulating oral uid ow. Patients
should not eat immediately before testing
because some food tends to inhibit oral
uid production. If blood is present in the
patient’s oral uid, collection of an alternative
specimen, such as blood or urine, would be
needed. Oral uid limits the number of repeat
or conrmatory tests on the specimen because
of the small amount of the sample, compared
with a urine sample.
Sweat
Several collection devices have been
manufactured for collecting sweat specimens.
The two most common are the patch and
the swipe; however, the sweat patch is the
only device approved by the U.S. Food and
Drug Administration (FDA). The quantity of
sweat collected is determined by the length
of time the patch is worn and the physiology
of the person wearing the patch. The patch
should be worn for at least 3 days, but no
longer than 7 days, although most drugs
will have been excreted within the rst 48
hours (Barnes et al., 2009; Huestis et al.,
2008; Kacinko et al., 2005; Schwilke et al.,
2006). This ensures that a sufcient amount
of sweat is collected for testing. The sweat
collected with the patch detects drug use that
occurred shortly before the patch was applied
and while the device remains on the skin.
The skin should be thoroughly cleaned with
soap and water and then swabbed well with
alcohol. The patch should then be applied to
the skin by a staff member, not the patient
(Watson et al., 2006). After 7 days, the patch
is removed by the practitioner and sent to the
laboratory for analysis.
Mainly the parent drug is found in sweat;
however, some drug metabolites also may
be detected (Dasgupta, 2008). Drugs and
drug metabolites that have been detected
21
Chapter 3―Preparing for Drug Testing
in sweat include tetrahydrocannabinol
(THC), amphetamine, methamphetamine,
methylenedioxymethamphetamine (MDMA,
or “Ecstasy”), codeine, morphine, heroin
metabolite, phencyclidine (PCP), and cocaine
and its metabolites (e.g., benzoylecgonine,
ecgonine methyl ester) (Barnes et al., 2009;
Dasgupta, 2008).
Because sweat can be collected only in
limited quantities, there may not be sufcient
specimen for repeat or conrmatory testing.
Sweat is less susceptible to tampering or
adulteration than is urine. The accuracy
of sweat testing is not standardized. Its
accuracy remains somewhat controversial
(Chawarski, Fiellin, O’Connor, Bernard, &
Schottenfeld, 2007; Watson et al., 2006) and
more research is needed (Barnes et al., 2009;
Huestis et al., 2008; Kacinko et al., 2005;
Schwilke et al., 2006). However, the sweat
patch is used extensively in the criminal
justice system, and its use to identify relapse
or violations of conditions of probation has
been upheld by the courts.
Blood
Blood testing detects alcohol or drug use
starting shortly after use, depending on the
substance and the route of administration. In
general, blood has a shorter detection period
than urine (Warner, 2003). Blood collection
is more invasive than other procedures and
requires trained personnel to collect the
specimen and perform laboratory testing. For
people who inject drugs, or those with poor
venous access, drawing blood may be difcult.
Hair
In theory, the presence of drugs in hair
is based on a simple principle: Drugs or
their metabolites circulate in a person’s
bloodstream, and the hair follicles absorb the
drug and/or metabolites from the bloodstream
and from secretions of the sebaceous and
sweat glands in the scalp (Cone, 1996;
Musshoff & Madea, 2006). Trace amounts
of drug become entrapped in the core of the
hair as it grows, at a rate of approximately
1 cm per month (Dolan et al., 2004). Drug
metabolites can be detected in the hair
shaft approximately 7–10 days after drug
ingestion. Hair is unique in that it may
provide retrospective information on drug
use, versus the point-of-time information
provided by urine, blood, and breath. (Kintz,
Villain, & Ludes, 2004). In some cases,
drugs were found to move down the hair
shaft via sweat (Henderson, Harkey, Zhou,
Jones, & Jacob, 1996), which would disrupt
the use of hair testing’s ability to determine
the historical use. Another unfortunate
aspect of interpreting hair test results of
drugs and their metabolites is that drugs
may be incorporated into hair by simple
environmental drug exposure (Ropero-Miller
& Stout, 2008; Wang & Cone, 1995).
The hair sample is usually taken from the
back of the head, cut with scissors as close to
the skin as possible (Wong & Tse, 2005). Hair
can be collected from other parts of the body
(e.g., face, armpit) of patients who are bald or
have shaved heads.
Hair testing appears to be most reliable for
detecting prior frequent, heavy use of cocaine,
opioids, amphetamine, PCP, and Ecstasy,
but is not suited for detection of very recent
use, or occasional drug use. Musshoff and
Madea (2006) report that hair tests can
detect the presence of the THC metabolite,
tetrahydrocannabinol carboxylic acid. Hair
analysis can often distinguish between
heroin and morphine use—a distinction that
is sometimes difcult to make with blood or
urine analysis (Dolan et al., 2004) because
of the short half-life of heroin metabolite in
these matrices. Hair testing for alcohol is
inappropriate; alcohol does not incorporate
into hair. However, the minor metabolites of
ethanol, ethyl glucuronide, and ethyl sulfate
in hair show promise as markers of alcohol
use (Wurst, Skipper, & Weinmann, 2003).
Clinical Drug Testing in Primary Care
22
Hair testing is suited to:
• Detecting chronic drug use (Dolan et al.,
2004; Warner, 2003);
• Providing a view of the patient’s long-term
substance use pattern; and
• Indicating periods of abstinence (Pragst &
Balikova, 2006).
An advantage of drug testing with hair is
the longer window of detection compared
with other matrices (Boumba, Ziavrou, &
Vougiouklakis, 2006). The detection period
for hair is limited only by the length of the
hair sample and the degree of deposition in
the hair. Cannabinoids have been shown to
deposit less readily than basic drugs in hair
(Huestis et al., 2007). Some laboratories
typically restrict analysis to a hair segment
representing about 3 months of growth.
However, this long window period is also a
disadvantage; hair testing is not useful in
substance abuse treatment or monitoring
opioid pain or other addictive medications
when frequent (weekly or monthly) drug
testing is desired. Because the timing of the
drug use is difcult to determine by testing
hair, it is not very useful clinically.
Disadvantages for testing for drugs in hair
are the high costs and the longer time needed
to obtain results, compared with the time
required by other matrices. Analysis of the
hair specimen is a complex process that
involves breaking down the hair to free the
drugs trapped in it. This chemical process
requires a longer time of analyses than other
matrixes. It can be done only in a laboratory;
no POCTs are available for testing hair
samples.
Some questions remain about environmental
contamination; a person may claim that
the drug is present in the hair because the
individual was in a room where others were
smoking drugs. Therefore, in preparation
for analysis at the laboratory, the hair
sample is washed, which may remove
the contamination. Unfortunately, this
environmental contamination cannot always
be differentiated from actual drug use, even if
drug metabolites are measured quantitatively
in hair (Ropero-Miller & Stout, 2008).
Additional controversies exist about whether
biophysical attributes affect hair analysis.
Studies have shown that concentrations of
drugs in hair can be affected by variations in
hair structure, growth rate, melanin content,
hygiene, and cosmetic hair treatments, such
as bleaching (Dasgupta, 2008). Although
there have been a limited number of human
clinical controlled studies, data show that
higher concentrations of some drugs (e.g.,
codeine, cocaine, amphetamine) are found
in dark hair compared with concentrations
found in blond or red hair (SAMHSA, 2004).
Cone and Joseph (1996) reviewed several
articles and found that hair testing may
be biased toward some hair types. Drugs
of abuse bind more readily to Africoid and
Mongoloid types of hair compared with
Caucasoid hair. Cosmetic hair treatments
also affect the binding of drugs to hair. For
example, bleaching of the hair can reduce
drug content, but it also can damage the hair
to the extent that bleaching may increase
binding of the drug to the hair (Skopp,
Pötsch, & Moeller, 1997). Some drugs (i.e.,
THC) do not differentially distribute into
hair based on melanin content (Smeal,
2007). Therefore, hair testing may not be
the most equitable drug testing matrix. Hair
rinses, bleaches, and shampoos that claim to
interfere with drug tests are advertised on
the Internet and in magazines.
Breath
Several simple-to-use, but accurate, breath-
testing devices are available for detecting
very recent alcohol use. Breath also may
be employed for the identication and
quantitation of a variety of other volatiles,
especially in industrial hygiene situations.
However, breath testing is commonly used
in alcohol treatment programs, but not in
primary care.
23
Chapter 3―Preparing for Drug Testing
•
The body metabolizes alcohol rapidly, but
alcohol will be detectable in breath as long
as it is present in blood. The detection period
for ethyl alcohol itself is hours (not days)
after the last alcohol use. The metabolism of
alcohol varies considerably by the person’s
gender, age, physical condition (especially the
condition of the liver), and weight.
Easily administered breath alcohol tests
are available to conrm alcohol ingestion
within the past several hours. When a breath
alcohol analyzer test is conducted properly,
it gives an accurate measurement of breath
alcohol content (BrAC). The BrAC gives an
estimate of blood alcohol level (BAL) (Watson
et al., 2006). Body temperature and breathing
patterns can affect breath alcohol test results.
Compared with blood and urine tests, breath
tests are less precise. Some evidence suggests
that breath tests may underestimate BALs by
approximately 8.5 percent (Garriott, 2008).
The breath alcohol analyzer (such as the
best-known version, Breathalyzer) is a device
that gives an accurate BrAC. The benets of
breath alcohol analyzers are that they:
• Are simple to use;
• Are inexpensive;
• Give instant results; and
• Are noninvasive.
The National Highway Trafc Safety
Administration provides a list of breath
alcohol analyzer devices that have been
tested for accuracy and reliability. The list is
available through http://www.dot.gov/odapc.
Meconium
Meconium is the rst few bowel movements
of a neonate. Research shows that meconium
provides a record of neonate exposure and
maternal substance use in the third trimester
of gestation (Concheiro et al., 2010; Gray
& Huestis, 2007; Kacinko, Jones, Johnson,
Choo, & Huestis, 2008). Meconium offers a
wide window of drug detection, monitoring
drug use primarily over the third trimester
of gestation. Because collection of meconium
is noninvasive (requiring only the transfer
of the specimen or meconium from diaper to
specimen container), it is usually easier to
collect than urine. Collection of a specimen
must be made before the neonate passes the
rst formed stool; for full-term babies, this
generally occurs within 3 days (Gareri, Klein,
& Koren, 2006).
However, this is a highly subspecialized
area that may be used in connection with
a maternal urine drug test. The testing of
meconium should be recognized as having
potential medicolegal ramications (i.e., a
positive test may result in the State removing
the newborn from the new mother’s custody).
Potential disadvantages to using meconium
exist. Test results vary greatly by substances
used and cutoff concentrations because of
the unique qualities of meconium. Moreover,
laboratory methods of preparing the specimen
can affect the test results greatly (Gray &
Huestis, 2007). Urine contamination may
skew results (Gray et al., 2010).
Selecting the Initial Testing Site:
Laboratory or Point-of-Care
Many factors should be considered when
deciding to test onsite with a POCT for the
initial test or offsite by a laboratory. Exhibit
3-2 compares POCTs and laboratory tests.
The sections below explain each method.
Collection Devices
The collection device must be single use. It
will normally be individually packaged with
collection aids and a tamper-evident security
seal. The collection device must not alter or
affect the specimen. The device should have
the following features for each specimen
matrix:
Blood. Sterile tubes that usually contain
sodium uoride to inhibit breakdown of
drugs. The use of “gel” or “serum separator
tubes” for specimen collection for any type
of drug analysis is highly discouraged.
• Hair. Foil or a plastic bag to store the
sample with an indication of proximal and
distal ends.
• Oral uid. Device that allows accurate
determination of the volume collected
(usually 1.0±0.1 mL) and that contains
an elution solvent to efciently elute the
adsorbed drugs.
• Sweat. A patch, placed on the skin,
typically composed of an adhesive layer,
release liner, and sweat-collection pad.
• Urine. A plastic collection container
typically with a temperature strip outside
the container to determine specimen
temperature.
Shipping materials, documentation, and
order forms will be needed if the specimen is
to be sent to a laboratory.
Exhibit 3-2. Comparison of Laboratory Tests and POCTs
Criterion Laboratory Test POCT
Time to Results Initial test can be available within hours,
but the confirmatory test takes days
Minutes
Ease of Use Requires complex equipment Relatively simple to use
Training Requires trained technicians or
technologists
Minimal training required
Breadth of Tests Wide range of test menus Limited test menu
Interpretation Objective quantitative results; variations
in laboratory cutoff concentrations may
influence interpretation
Subjective results; requires interpretation,
not quantitative
Sources: Melanson (2005); Watson et al. (2006).
Clinical Drug Testing in Primary Care
24
Laboratory Tests
Laboratories perform screening,
conrmatory, and validity tests, using
instrumented devices that are operated by
trained technical personnel. Laboratory
testing is more accurate than POCT and
provides quantitative information on what
drugs and/or metabolites were detected.
Laboratories use high-volume immunoassay
tests to separate negative specimens from
those that require conrmation testing.
Conrmation tests use either liquid
chromatography (LC) or gas chromatography
(GC) in combination with mass spectrometry
(MS) for detection and measurement of drugs
and metabolites. Tandem mass spectrometry
(MS/MS) is a more sensitive form of MS.
These tests provide a laboratory with the
ability to identify and measure drugs and/
or metabolites in biological uids at low
concentrations. Technical details about these
tests and their strengths and limitations are
in Appendixes B–D.
Most laboratories usually perform initial
drug tests for commonly abused drugs,
including 6-acetylmorphine (heroin
metabolite), opioids, cocaine, amphetamines,
barbiturates, PCP, and THC. Some
laboratories offer extended opioid panels;
these laboratory tests can detect and conrm
several opioids including morphine, codeine,
hydrocodone, hydromorphone, oxycodone,
and oxymorphone. Some laboratories offer,
upon request, panels that will differentiate
individual benzodiazepines and their
metabolites.
Other extended panels include
buprenorphine, carisoprodol, methadone,
fentanyl, meperidine, and propoxyphene,
among others. Not all laboratories
are capable of identifying all known
benzodiazepines and, where necessary
or appropriate, their metabolites. The
requirement for additional testing depends
in large part on the patient population
25
Chapter 3―Preparing for Drug Testing
•
served by the facilities using the laboratory
(e.g., a methadone clinic or a detoxication
facility might require methadone, EDDP
[methadone metabolite], burprenorphine/
norbuprenorphine, and/or other drug or
metabolite analyses). POCTs or laboratory-
based tests may be used for the initial
testing, but only laboratories can perform
conrmatory testing.
Advantages and Disadvantages of Testing
in a Laboratory
Advantages. Laboratory tests have
several important advantages over POCTs.
Laboratory tests:
• Generally have a higher degree of precision.
• May offer quantitation of drugs and/or
metabolites and a reasonable estimate of
the timeframe in which the drug was used.
• Can provide information on specic drugs
used.
Can be directly sent for conrmatory
GC/MS on the same sample.
• Are performed by trained laboratory
professionals.
Disadvantages. The disadvantage of
laboratory-based tests is turnaround time.
The time required for laboratory-based
testing may include transportation of the
specimen to the laboratory, specimen aliquot
preparation, and instrument analysis time—
steps that are not required for POCTs.
Results from POCT can be available while the
patient is still in the ofce, so the practitioner
can immediately discuss them with the
patient. Depending on the laboratory, clinical
screening results may be available in less
than 1 hour after receipt or the next day,
unless further testing, such as conrmation
or reexive testing, is required.
Considerations for Selecting a Laboratory
Before selecting a laboratory, practitioners
should contact the laboratory and speak
directly to the director or toxicologist to
(White & Black, 2007):
• Determine the laboratory’s analytic
capabilities (laboratories may use the
Federal Five as the testing menu for drug
screens, which may or may not include the
clinical drugs of interest);
• Inquire about other panels that test for
drugs and drug classes of clinical interest;
• Conrm that the laboratory follows
established Federal and State regulations
(Exhibit 3-3);
• Determine whether the laboratory’s testing
procedures are appropriate for clinical use;
and
• Ensure that the laboratory provides
technical assistance so the practitioner can
obtain help with interpreting test results
or determining which panel to order.
Exhibit 3-3. Federal and State Regulations
• The Clinical Laboratory Improvement
Amendments (CLIA) of 1967 and of 1988 set
forth conditions that all laboratories must meet
to be certified to perform testing on biological
specimens (http://www.cms.gov).
• The U.S. Department of Health and Human
Services (HHS) Mandatory Guidelines for
Federal Workplace Drug Testing Programs
specify the requirements for a laboratory to
be certified by the HHS National Laboratory
Certification Program. Information is available
at http://workplace.samhsa.gov/Dtesting.html
• Private and professional organizations (e.g.,
College of American Pathologists) have
established voluntary laboratory accreditation
programs. The American Association of
Bioanalysts has private personnel standards.
• State clinical laboratory programs operate
under individual State laws; State programs
are usually authorized through the Centers for
Medicare & Medicaid Services.
Clinical Drug Testing in Primary Care
26
•
Practitioners need to talk to laboratory
personnel about:
• Appropriate in-ofce specimen collection,
handling, and storage procedures for each
matrix used;
• Each test ordered, at least until the
practitioner is thoroughly familiar with the
tests and drug panels the laboratory offers
(practitioners need to be sure they know
exactly what they are ordering and the
limitations of any particular test);
• Test results (practitioners should contact
the laboratory about unexpected results,
whether positive or negative); and
• Referral testing for drugs not offered by
the primary testing clinical laboratory.
Point-of-Care Tests
Several different types of POCTs are
available. Generally, POCTs:
• Use well-established immunoassay
technologies for drug detection;
• Determine the presence of parent drugs or
their metabolites;
• Sometimes can determine the validity
of a specimen, which is to be highly
recommended as an integral part of the
testing process;
• Identify drug classes (e.g., opioids,
benzodiazepines, barbiturates),
single drugs, or metabolites (e.g.,
benzoylecgonine, a cocaine metabolite); and
Require a few drops of a specimen.
FDA has approved POCT devices for urine,
breath, and oral uid testing, but devices
for urine drug testing are most widely used.
Advances are being made in developing
POCTs for other matrices, and these may be
available in the future.
Various POCTs are available:
• Breath-testing devices, which are rare in
primary care practice (the patient blows
into the device)
• Cards or cassettes (drops of urine are
placed on a card or in wells on a cassette)
• Dipsticks (an absorbent strip is dipped into
the specimen)
• Combination collection/test cups (the
testing strip is integrated into the
collection cup, and results can be read on
the outside of the cup)
A few devices double as both collection
and testing devices. After the specimen
is collected, the tester initiates the test,
carefully times the test, and interprets and
records the results. The test component of
noninstrumented POCTs is an absorbent
strip with an antibody-dye complex. The test
is done by inserting the absorbent strip, card,
or cassette into the specimen or adding the
specimen to the testing device. When the
strip or cassette comes into contact with the
specimen, it reacts to the drug or drug class
that the POCT can detect. Generally, a line or
dot appears in the zone labeled for a specic
drug if the drug is not present (negative
test result); no line or dot appears when a
specic drug is present (positive test result).
A photocopy of the portion of the POCT device
that is read can be made and placed in the
patient’s chart. Enough uid (urine or oral
uid) should be retained for any reexive or
conrmatory testing that may be required.
It is critical that practitioners read package
inserts carefully to know how to perform
the test and read the results. Positive POCT
results should usually be followed by a
laboratory conrmatory test if the patient
denies drug use when confronted with the
positive results. A conrmatory test must be
done if legal or employment ramications for
the patient will result.
27
Chapter 3―Preparing for Drug Testing
Advantages and Disadvantages of POCTs
The principal advantage of POCTs is that
the results are available in approximately
10 minutes. This fast turnaround allows
practitioners to discuss the results with the
patient during that ofce visit and make
clinical decisions and act appropriately that
day. This early intervention may prevent
other health problems, hospitalization, or
treatment episodes. It is also in keeping
with behavioral principles: the immediacy
of the intervention in relation to a behavior
makes reinforcement more useful. Several
manufacturers have developed drug-of-abuse
assays for POCT that offer similar, but
not exact, sensitivity and specicity to the
methodologies used by central laboratories
(Melanson, 2009). A variety of testing
panels with different cutoff concentrations
is available for these testing devices, but
they are not as varied as laboratory testing.
Increasingly, vendors are offering point-
of-care devices that test for a wider range
of drugs and with more sensitivity and
specicity. POCTs are available to test
for amphetamine, methamphetamine,
barbiturates, benzodiazepines, cocaine,
methadone, opioids, PCP, propoxyphene,
Ecstasy, oxycodone, tricyclic antidepressants,
buprenorphine, and THC acid metabolite
(Melanson, 2005).
A survey of ve POCT immunoassay
devices for urine testing found that each
had a false-negative rate for opioids of less
that 1 percent and a false-positive rate
less than 0.25 percent for testing for pain
management (Crouch, Hersch, Cook, Frank,
& Walsh, 2002). Melanson’s (2009) review
of the literature reviewed studies looking
at the analytical performance (sensitivity,
specicity, precision, and accuracy) of
POCTs for drugs of abuse. Generally, most
studies suggested that POCTs are a reliable
method to screen for drugs of abuse and
that the results are comparable to those
from automated immunoassays and GC/MS.
However, Melanson (2009) also noted that
some studies found inconsistencies, such as:
• Several devices were found to have
discrepancies between the claims of the
manufacturer and the devices’ product
performance.
• Some devices deviated from their stated
cutoffs showing positive results below the
cutoff or negative results above the cutoffs.
However, no POCT device yields perfect
agreement with more sophisticated testing,
such as GC/MS or high-performance liquid
chromatography (Watson et al., 2006).
Disagreement between methods was highest
for samples near the cutoffs.
Cross-reactivity differs among POCT devices
because of differing antibody specicity. The
manufacturer provides a list of compounds
tested and their degree of cross-reactivity,
including those medications outside the drug
class, which may cause false-positive results
(Melanson, 2009).
George and Braithwaite (2002) caution
that the apparent benet of POCTs—rapid
assessment of a patient’s drug use—can be
detrimental if treatment decisions are based
on these rapid, but unconrmed, results. A
disadvantage of noninstrumented POCTs
is that most test only for drug classes, not
for specic drugs within a class (Gourlay,
Caplan, & Heit, 2010), which is what is
needed more often in clinical applications.
Many POCTs have a limited test menu,
compared with laboratory testing and
in clinical settings; practitioners may
need a more complete panel, or separate
tests, to assess for specic drugs. POCT
devices do not provide quantitative drug
or metabolite information. POCT devices
provide presumptive results only; a sample
needs to be sent for conrmatory testing at a
laboratory. Cutoffs employed by some POCT
devices may not provide adequate sensitivity.
Result interpretation may also be subjective,
making performance operator-dependent
(Melanson, 2009).
Clinical Drug Testing in Primary Care
28
Considerations for Selecting POCT Devices
Matrices. POCT devices should be FDA
approved and usually CLIA-waived to test
urine, breath (for alcohol), and oral uid for
substances of abuse. None are available yet
for hair, sweat, or blood for drugs of abuse,
although some POCT devices do exist for
therapeutic drugs in blood or blood products.
POCTs for urine remain the most commonly
used, despite advances in testing of other
matrices. Cutoff levels, cross-reactivity,
and other possible interferences have been
studied more for POCT urinalysis than for
any other matrix (Watson et al., 2006). Most
POCT devices are used in an environment
that is external to a clinical laboratory.
Regulatory Issues. The use of POCTs is
covered by two Federal regulations. The
Medical Devices Act requires that all in vitro
medical diagnostic devices be evaluated
and cleared for use by FDA for commercial
distribution before use with patients. CLIA
regulates the use of POCTs and requires
that medical diagnostic tests and devices be
used only in laboratories that meet CLIA
standards and are certied to perform those
specic tests. However, tests may be waived
from CLIA regulatory oversight if they meet
certain requirements, primarily if they are
simple to use and interpret and have a low
error risk.
Practitioners should be aware of the following
specic requirements when considering using
a POCT device:
• FDA approval. FDA has cleared several
point-of-care devices for testing drugs of
abuse. The FDA Center for Devices and
Radiological Health provides information
on test categorization and approval or
clearance of testing devices (http://www.
fda.gov/MedicalDevices/default.htm).
• Waived tests. A testing device may have
been cleared by FDA for commercial
distribution, but may not have been CLIA
waived. FDA maintains a list of currently
waived tests (http://www.accessdata.fda.
gov/scripts/cdrh/cfdocs/cfCLIA/testswaived.
cfm). POCT manufacturers will also state
whether a test is waived by CLIA.
• Certicate of waiver. All sites
performing waived tests must have a
CLIA-waiver certicate and adhere to the
manufacturer’s instructions for performing
the test. Facilities or physicians’ ofces
performing waived tests must enroll in
CLIA, pay the applicable fee, and follow
the manufacturer’s instructions. An
explanation of the procedures to obtain a
CLIA certicate is available at
https://www.cms.gov/Regulations-and-
Guidance/Legislation/CLIA/downloads/
HowObtainCerticateofWaiver.pdf.
• State regulatory issues. Many States
have their own regulations regarding POCTs
that practitioners or their designees must
learn before they start to test.
Cost. The information on the economics
of POCT for drugs and ethanol is limited,
although cost issues should be important in
deciding to initiate a point-of-care drug-testing
program. The xed unit price of POCTs
often exceeds those of laboratory-based test
methods. However, the cost of devices also
depends in large part on the number of drugs
included in the test panel, the difculty
in identifying the substances included in
the panel, the number of devices ordered,
and the volume of testing. Costs may vary
according to location. In general, as the
demand for POCTs grows, the cost per
device decreases. In addition, the extra staff
time and space to perform the test, staff
training, quality assurance procedures, and
documentation need to be taken into account
when considering the cost. Then again, staff
already collect specimens and perform POCTs
to test for other conditions in many physician
practices. These costs should be carefully
reviewed prior to initiating POCT for drug
testing.
29
Chapter 3―Preparing for Drug Testing
•
•
•
•
•
•
Other Considerations. Practitioners should
research the point-of-care devices being
considered for use in terms of (Melanson,
2005):
• Analytic performance. Seemingly minor
differences in sensitivity, specicity, and
accuracy among the available POCT
devices may or may not be clinically
important and must be evaluated.
Cross-reactivity. Some devices may
not be able to distinguish between the
substance being tested for and other
chemically similar substances.
Validation studies. Lot-specic evaluation
information is usually summarized in
package inserts, with more extensive
verication documentation available on
request. A POCT manufacturer may have
additional credentials documenting that
the testing device and the manufacturing
processes meet quality control and quality
assurance standards (e.g., certication
by the International Organization for
Standardization).
Ease of use. Most POCT devices can
be operated by an individual with little
laboratory experience. However, some
devices may entail following fairly complex
instructions for use, which can contribute
to human errors that will affect test
results. Even test operators with technical
or scientic backgrounds can make errors
using these devices because of lack of
training or unfamiliarity with new devices.
Ease of reading and interpreting
the results. Most devices require visual
interpretation of a color response. Clear,
distinguishable results are necessary
for accurate interpretation. It is also
necessary to know which substances will
cross-react and produce a false-positive
result (e.g., pseudoephedrine giving
an “amphetamines” positive
) or a false
negative result (e.g., oxycodone and its
active metabolite oxymorphone, both
of which are opiates, giving a negative
opiates result when either or both are
present in the patient’s specimen).
Quality assurance and control
procedures. Devices differ in the amount
of time needed for staff to learn quality
control procedures, such as completing
documentation to ensure adherence
to the manufacturer’s instructions for
maintenance (if any) and assay of the
appropriate control specimens at the
required intervals. Maintenance and
quality control procedures also must meet
CLIA, State, and local regulations. Positive
and negative quality control samples must
be included to verify accurate testing, but
the frequency of analysis of quality control
is dependent upon State regulations or
regulatory agency.
Laboratory testing for verication.
It is suggested that a percentage (i.e., 5
percent) of specimens that screen negative
or positive be sent to a laboratory to verify
accurate performance of POCT results, and
that all positive results that are contested
by patients be submitted to a laboratory
for conrmation testing.
Implementing Point-of-Care Testing
Based on surveys of sites holding CLIA
waivers, Howerton, Anderson, Bosse,
Granade, and Westbrook (2005) suggest that
practitioners consider the following questions
when deciding whether to use any type of
POCT device:
• Who will manage and be accountable for
testing oversight? Can this person receive
the appropriate training?
• Are there sufcient personnel to conduct
testing?
• How will testing affect workow?
• How will staff be trained to conduct a
POCT?
• Can the site adequately comply with
Federal, State, and local regulations
regarding the POCT?
• What are the safety considerations for both
personnel and patients?
Clinical Drug Testing in Primary Care
30
• Can personnel reasonably follow quality
control procedures?
• Does the site meet physical requirements
for testing (e.g., space for collection,
testing, storage, security)?
• What are the benets and costs of POCTs
to the practitioner?
• How will testing records be maintained?
What written documentation is needed?
• What are the plans for quality control
testing and quality assurance?
Preparing Clinical and Office Staffs for
Testing
Once a practitioner has decided which
matrices and types of tests to use, the clinical
and ofce staffs need to be prepared to begin
testing. Preparation may include:
• Obtaining a CLIA waiver;
• Developing written policies and procedures
for testing, including ongoing staff
training, and establishing quality control
procedures;
• Developing and implementing testing
protocols, including guidelines for
specimen collection, use of POCT,
conrmatory testing, and laboratory
technical assistance;
• Establishing condentiality safeguards;
• Training staff in use of the selected POCT
devices and in collecting specimens for
laboratory testing;
• Establishing recordkeeping procedures;
• Preparing appropriate storage sites for
completed POCTs and laboratory tests;
and
• Arranging pickup or transportation for
laboratory tests.
Preparing a Specimen Collection
Site
The collection site is a designated area where
a patient provides the specimen for a drug
test. Collection of most specimen matrices
does not require special arrangements. Urine
collection in primary care settings needs
to be congured for privacy while a patient
provides a specimen if direct observations
are not required. Water for drinking needs to
be available in the event the patient cannot
provide sufcient urine (shy bladder). In
substance abuse treatment and workplace
testing, measures need to be taken to prevent
adulteration or substitution, such as putting
a bluing agent in the toilet, not providing
access to soap and water in the collection
room, and directly observing specimen
provision. These actions are needed in clinical
situations only if adulteration or substitution
is suspected. Once specimens are collected
and labeled, there must be space and proper
conditions for securely and appropriately
storing them. A refrigerator is a convenient,
appropriate storage place, especially when
samples are picked up by a laboratory courier
on a daily or less frequent basis.
31
Chapter 4—Drug Testing in Primary Care
In This Chapter
• Uses of Drug Testing
in Primary Care
• Talking With Patients
About Drug Testing
• Cultural Competency
and Diversity
• Monitoring Patients
• Ensuring
Condentiality and 42
CFR Part 2
• Preparing for
Implementing Drug
Testing
• Interpreting Drug
Test Results
• Frequency of Testing
• Documentation and
Reimbursement
Uses of Drug Testing in Primary Care
Primary care providers order a wide array of laboratory tests
as part of routine physicals and to determine the cause of
symptoms, adjust medication dosages, monitor treatment
effectiveness, and diagnose. Drug tests can be ordered and
used for these same reasons.
Discussing substance use with patients can be time-consuming
and may upset some patients. However, if a drug test is
indicated, talking with patients before, after, and even if drug
testing is refused can yield information that may improve
many aspects of primary care. Some examples of when the
use of drug testing or discussing substance use could improve
patient care include:
• Evaluating unexplained symptoms or unexpected responses
to treatment and identifying substance use that has
contributed to, caused, or is complicating the patient’s
treatment;
• Evaluating patients in psychiatric care for substance abuse
issues, or before prescribing psychoactive medications;
• Identifying potential substance use problems in women
who are pregnant, or planning on becoming pregnant, and
identifying at-risk neonates;
• Identifying patients with possible substance abuse issues;
• Monitoring patients in substance abuse treatment: to
assess the efcacy of the treatment plan and the level
of care, to monitor abstinence before administering
medications to treat substance use disorders (SUDs),
and to help identify a relapse to substance use;
• Ensuring patient safety prior to surgery or other invasive
procedures to prevent medication interactions;
• Managing patients prescribed opioids for chronic pain
control; and
• Monitoring potentially addictive prescription use (e.g.,
sedatives, tranquilizers, medications to treat attention-
decit/hyperactivity disorder [ADHD]).
Clinical Drug Testing in Primary Care
32
Monitoring Prescription Medication Use
Drug testing is useful for monitoring patient
treatment compliance with prescribed
medications that have addictive properties
(e.g., opioid pain medication, sedatives,
ADHD medication). Test results can reveal
whether patients have recently taken their
prescribed medication and if non-prescribed
or illicit drugs have been used. Drug testing
can help practitioners identify and reduce
diversion of scheduled drugs by patients.
Management of Chronic Pain With Opioids
Primary care practitioners often provide
medical management for patients taking
opioids for chronic pain. Long-term pain
treatment with opioids requires monitoring
for continuing effectiveness for pain relief
and the potential for misuse, addiction,
or diversion. Current clinical guidelines
recommend the use of drug tests for pain
management with opioids to help guide
decisions about prescribing scheduled
medications, revising treatment regimens,
and when to initiate or refer for substance
abuse treatment (Chou et al., 2009; Fishman,
2007).
Gourlay, Caplan, and Heit (2010) suggest
that drug testing may be useful for:
• New patients as part of regular care to
indentify the use of illicit or nonprescribed
drugs;
• Patients being prescribed a controlled
substance;
• Patients who present with a condition that
warrants a prescription for a controlled
substance and who resist a full evaluation
or who request a specic medication with
addictive potential;
• Patients with aberrant behavior
(e.g., patients who consistently want
appointments toward the end of ofce
hours, arrive after ofce hours, insist on
being seen immediately, repeatedly report
losing prescriptions or medications, are
reluctant to change medication, do not
adhere to the treatment plan);
• Patients who are suspected of diversion;
• Patients who need advocacy to verify their
abstinence;
• Patients in recovery from SUDs; and
• Patients who need a change in their
treatment.
Katz and colleagues (2003) conducted a
3-year study on behavioral monitoring and
urine drug testing in patients receiving
long-term opioid therapy for pain. Their
ndings suggest that random drug testing
of all patients receiving opioids for pain
may be warranted. The researchers found
that urine drug testing was much more
effective than behavioral monitoring alone
in identifying patients who were taking
drugs other than the prescribed opioid.
For example, 72 percent of patients with
a positive test result did not have any
behavioral indicators considered useful for
screening.
Evaluation of Unexplained Symptoms or
Unexpected Responses to Treatment
The results of drug tests can clarify situations
in which substance use contributes to, causes,
or complicates diagnosis or treatment, but the
substance use is not apparent to the clinician.
Patients may not disclose:
• All the medications prescribed by other
providers or over-the-counter (OTC)
medications and herbal products;
• That they take medications prescribed for
other people;
• Use of illicit drugs or how much alcohol
they consume; or
• If they have stopped taking their
medications.
33
Chapter 4—Drug Testing in Primary Care
Following are some clinical examples of when
or where drug testing might explain the
cause of symptoms or unexpected response to
treatment:
• A man whose hypertension remains
uncontrolled, despite adhering to a
low-salt diet and several antihypertensive
medication changes, who does not inform
the clinician that he drinks more than four
drinks almost every evening and more on
weekends.
• A college student who complains of heart
palpitations, but does not mention using
her roommate’s medication for ADHD to
help her study.
• An elderly woman who is increasingly
confused and somnolent and has a normal
physical, tests, and laboratory results, but
does not state that she self-medicates with
her friend’s prescribed benzodiazepines to
help her “nerves.”
• A patient with pancreatitis who repeatedly
denies alcohol use and is negative for any
other causes.
In clinical situations, such as these and others,
practitioners can order drug tests and use the
results to gain a better understanding of the
true clinical picture, determine the diagnosis,
talk to the patient, and then work more
effectively with the patient.
Patient Safety
In some cases, ensuring patient safety is
the primary reason for testing in clinical
situations. For example:
• Preoperative or preprocedure
evaluations. Primary care providers
often do evaluations for their patients
prior to planned surgery or other invasive
procedures. Drug tests may identify
medication or illicit drug use not disclosed
during the practitioner–patient interview.
Drug testing can be used if the practitioner
suspects that the patient is using drugs,
or if the patient has a history of drug use.
The primary care physician can alert the
anesthesiologists or radiologists to the
possible presence of substances that could
cause adverse drug reactions, interfere
with anesthesia, prevent possible cardiac
complications or respiratory depression,
prevent the patient from experiencing
withdrawal if hospitalized, or experience
poor pain management if the patient has
been taking high doses of opioids and has
developed tolerance.
• Preventing toxic drug interactions.
Drug testing may reveal a patient’s use of
multiple substances, both legal (prescribed
and OTC medications) and illicit drugs. A
practitioner needs this information before
prescribing a new medication or starting
pharmacotherapy for SUDs, psychiatric
conditions, and other health problems. For
example, a toxic interaction can occur if a
patient uses other central nervous system
depressants while taking buprenorphine or
methadone.
Pregnancy
Drug and alcohol testing of women who are
pregnant or who want to become pregnant
is an opportunity to prevent damage to the
woman and the fetus. During preconception
counseling, women should be advised about
the risks of alcohol, tobacco, and drug use to
the fetus. Screening for substance use should
be done so that the patient can be assessed
and referred to treatment before becoming
pregnant. SUD screening and assessment of
a pregnant woman can identify an SUD early
enough for intervention and for preventing,
minimizing, or at the very least preparing
for serious problems for the fetus or neonate.
Pregnant women should be strongly urged
to abstain from alcohol and drugs, and, if
necessary, referred to treatment as soon as
possible. Drug testing can be used to monitor
abstinence.
A difcult dilemma is created by State laws
that require the reporting of nonmedical
use of controlled substances by a pregnant
woman or that require drug testing after
delivery if illicit drug use is suspected.
These laws can have the unintended effect
Clinical Drug Testing in Primary Care
34
of women not seeking prenatal care. Drug
testing during pregnancy, or postnatally,
can have severe consequences. In many
States, pregnant and parenting women
can be reported to child protective services,
even though the courts have struck down
criminal charges against women who are
pregnant and use drugs. Women have the
right to refuse drug testing (American College
of Obstetricians and Gynecologists, 2008);
however, if drug abuse is suspected that is
contributing to child abuse, reporting to child
protective services is necessary.
Psychiatric Care
Drug testing is uncommon for patients
who are primarily being treated for mental
disorders, but should be considered when
assessing a patient presenting with mood or
behavior changes (Black & Andreasen, 2011).
Drug tests could be used with patients with
possible mental disorders to aid in diagnosis,
help determine whether the psychiatric
symptoms are substance use or withdrawal
related, or to identify a co-occurring SUD.
Controlled substances are prescribed for some
psychiatric conditions (e.g., benzodiazepines
for chronic anxiety disorder or stimulants for
ADHD). Drug test monitoring for adherence
to controlled medications may be indicated
for some patients.
Monitoring Office-Based Pharmacotherapy
for Opioid Use Disorders
The Drug Addiction Treatment Act of 2000
(DATA 2000) permits ofce-based substance
abuse treatment by allowing certied
physicians to prescribe Schedule III, IV, and
V medications to treat opioid dependence. To
prescribe buprenorphine, a Schedule III
opioid medication, physicians must qualify
for a DATA 2000 waiver. Physicians
providing ofce-based pharmacotherapy use
drug testing to monitor compliance with
pharmacotherapy and abstinence from illicit
opioids. For more information, visit http://
buprenorphine.samhsa.gov/index.html
and see Treatment Improvement Protocol
(TIP) 40: Clinical Guidelines for the Use of
Buprenorphine in the Treatment of Opioid
Addiction (Center for Substance Abuse
Treatment [CSAT], 2004).
Detection of Substance Use Disorders
Many patients seeing primary care providers
have an undiagnosed SUD and providers can
play important, preventive roles in detecting
and addressing SUDs in the primary care
setting. Drug testing can aid the provider
in identifying those patients using illicit
substances and screen them further for a
possible SUD. It must be noted that a positive
drug screen is not diagnostic in itself of an
SUD.
The practitioner can nd clues for a possible
SUD in a patient’s laboratory ndings,
physical examination, and medical history.
For example, liver enzyme abnormalities may
suggest current or past alcohol misuse or
dependence, and hepatitis B and C antibodies
can suggest current or past drug use. A
physical examination may reveal track marks
or abscesses, or a patient may have a history
of medical conditions that suggests an SUD
(e.g., cirrhosis, pancreatitis). Other physical
signs include frequent falls or injuries,
bruises the patient cannot explain, physical
complaints without corresponding physical
ndings, deterioration in personal hygiene,
and disheveled appearance.
Physical signs of SUDs may not appear
until late in the progression of the disorder.
Nonphysical or behavioral signs could
include:
• Reports of marital, academic, or
employment problems;
• Chaotic lifestyle;
• Deterioration in grooming or hygiene;
• Unusual mood swings or outbursts;
• Money or other valuable items missing
from the home;
35
Chapter 4—Drug Testing in Primary Care
• Requests for specic potentially addictive
medications; and
• Frequent reports of losing prescriptions
for potentially addictive medications.
Initial Assessment of a Person With a
Suspected SUD
A positive drug test does not necessarily
indicate a diagnosis of an SUD. The drug use
could be sporadic and not meet the diagnostic
criteria in the Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition,
Text Revision (American Psychiatric
Association, 2000). These patients will need
screening and assessment. When informing
a patient about the test results of an initial
assessment, the practitioner can:
• Inform the patient about the health and
medical consequences (Fleming, 1995).
Once screening results are explained,
describe the health risks and medical
consequences of use of the substance
in question. For some (e.g., people with
chronic hepatitis) any consumption of a
substance, such as ethanol, may be unsafe.
Likewise, the use of stimulants, such as
cocaine and amphetamines, could have
disastrous consequences for a patient
with compromised cardiac function or
hypertension. Women who are pregnant
or who want to become pregnant should
be told of the dangers an SUD poses to
the fetus and the mother, receive further
assessment, or be referred to SUD
treatment.
• Pay careful attention to semantics.
Avoid pejorative labels of “alcoholic” or
“addict.” Use neutral, nonstigmatizing
language (e.g., “people with substance
use problems”). Do not use humiliating or
confrontational approaches to try to force
the patient to agree to treatment.
• Recognize that a positive test result may
trigger patient resistance or feelings of
guilt, shame, or anger. Avoid arguing
with the patient. Negative reactions can
often be countered by focusing on the
relationship between the original health
complaint and the patient’s use of drugs or
alcohol.
• Demonstrate an understanding and
acceptance of the patient and communicate
that the clinician will help the client help
himself or herself.
• Address goals and strategies for change.
Assess the patient’s readiness for change.
Help the client clarify the nature of his
or her difculties. Express empathy and
a willingness to listen to the client. Use
motivational counseling approaches to
encourage further screening or assessment
or treatment options. Foster hope for
positive change. Resources for more
information about motivational approaches
are in Exhibit 4-1.
A positive test result for illicit drugs or
nonprescribed licit medications does not
necessarily mean that the patient has an
SUD; it means that the SUD may exist and
the patient needs further screening to rule
out an SUD or determine whether an SUD
assessment is needed. The practitioner can
do brief ofce-based screening, using the test
result to start a discussion. The practitioner
can also use a screening instrument; the
simplest and quickest screening instrument
is CAGE-AID (Exhibit 4-2). CAGE-AID is a
tool that has been tested with primary care
patients (Brown & Rounds, 1995).
Exhibit 4-1. Motivational Interviewing
Resources
• TIP 35: Enhancing Motivation for Change in
Substance Abuse Treatment (CSAT, 1999b)
• KAP Keys for Clinicians Based on TIP 35
(CSAT, 2001a)
• Quick Guide for Clinicians Based on TIP 35
(CSAT, 2001b)
• Motivational Interviewing: Preparing People
for Change (Miller & Rollnick, 2002)
• The Motivational Interviewing Page
(http://www.motivationalinterview.org)
• Helping Patients Who Drink Too Much: A
Clinician’s Guide, Updated 2005 Edition
(National Institute on Alcohol Abuse and
Alcoholism, 2007)
Clinical Drug Testing in Primary Care
36
•
•
Exhibit 4-2. The CAGE-AID Questions
1.Have you felt you ought to Cut down on your
drinking or drug use?
2.Have people Annoyed you by criticizing your
drinking or drug use?
3.Have you felt bad or Guilty about your
drinking or drug use?
4.Have you ever had a drink or used drugs first
thing in the morning to steady your nerves or
to get rid of a hangover (Eye-opener)?
The National Institute of Drug Abuse’s
(NIDA’s) NIDAMED provides resources for
health professionals and is available at http://
www.nida.nih.gov/nidamed/screening/.
The NIDAMED Web site includes a number
of resources, such as:
NIDA’s Clinician’s Screening Tool,
NIDA-Modied Alcohol, Smoking, and
Substance Involvement Screening Test
(NMASSIST), is available online and in
hard copy.
Resource Guide: Screening for Drug Use
in General Medical Settings provides
information on using the 5As–Ask, Advise,
Assess, Assist, and Arrange.
NMASSIST is a well-validated tool in general
medical settings. The empirical evidence is
good for screening and brief intervention for
alcohol use disorders in a primary care
setting, but it is more limited for the treatment
of drug use disorders, which might require a
more intensive care setting.
Several screening and assessment tools
are listed in Appendix C—Screening and
Assessment Instruments in TIP 24: A Guide
to Substance Abuse Services for Primary Care
Clinicians (CSAT, 1997).
When screening or a brief assessment
indicates a problem with substance use,
the practitioner may want to try brief
ofce-based interventions. A brief
intervention is a pretreatment tool or
prevention technique that involves
ofce-based, practitioner-patient contacts
of 10–15 minutes for a limited number
of sessions. The number and frequency
of sessions depend on the severity of the
problem and the patient’s response. A brief
intervention can be useful before or after
an indepth assessment and both during
and after specialized treatment as part of
followup and relapse prevention. Exhibit 4-3
lists basic elements of brief interventions
using FRAMES. More indepth information
can be found in TIP 34: Brief Interventions
and Brief Therapies for Substance Abuse
(CSAT, 1999a); TIP 24: A Guide to Substance
Abuse Services for Primary Care Clinicians
(CSAT, 1997); Brief Intervention for
Hazardous and Harmful Drinking: A Manual
for Use in Primary Care (Babor & Higgins-
Biddle, 2001); and at the Substance Abuse
and Mental Health Services Administration’s
(SAMHSA’s) Web site on screening, brief
intervention, and referral to treatment http://
www.samhsa.gov/prevention/SBIRT/index.
aspx.
Exhibit 4-3. Brief Intervention Elements:
FRAMES
Feedback—The practitioner gives patients
personalized feedback relevant to their
individual situation.
Responsibility—The practitioner lets patients
know that they are ultimately responsible for
their recovery.
Advice—Studies have proved that even brief
sessions providing information or advice about
substance use can lead to behavior changes
(Rollnick, Heather, & Bell, 1992).
Menu—Giving patients a menu of strategies (as
appropriate to the treatment situation) adds to
the sense of responsibility patients feel.
Empathy—An empathetic approach to
treatment has been positively linked to positive
treatment outcomes.
Self-Efficacy—The feeling of self-efficacy (e.g., I
can change) is critical to promoting behavioral
changes in patients. Patients’ belief that they
are capable of changing their behavior can help
them through challenging parts of recovery.
Source: Miller & Sanchez (1994)
37
Chapter 4—Drug Testing in Primary Care
If a practitioner suspects an SUD, he or
she can refer the patient to appropriate
psychosocial or medication-assisted treatment
services. Often, making a telephone call to
a treatment facility while the patient is in
the ofce is the best way to get a patient
to treatment. Substance abuse treatment
providers will do a thorough assessment and
recommend the least intensive environment
that is safe and effective for the patient.
The practitioner should follow the patient’s
progress in treatment and request evidence
of the patient’s adherence to prescribed
psychosocial services. Brief interventions can
be successful. The patient could also have
drug tests during subsequent visits to assess
progress. Exhibit 4-4 provides a owchart of
the screening, assessment, brief intervention,
and referral processes in primary care
settings.
Exhibit 4-4. Patient Flow Through Screening and Referral in Primary Care
Clinical Drug Testing in Primary Care
38
For more information, refer to the following
publications:
• TIP 24: A Guide to Substance Abuse
Services for Primary Care Clinicians
(CSAT, 1997)
• TIP 40: Clinical Guidelines for the Use of
Buprenorphine in the Treatment of Opioid
Addiction (CSAT, 2004)
• TIP 49: Incorporating Alcohol
Pharmacotherapies Into Medical Practice
(CSAT, 2009)
• Screening for Drug Use in General Medical
Settings, Quick Reference Guide (NIDA,
2009)
• Helping Patients Who Drink Too Much: A
Clinician’s Guide (National Institute on
Alcohol Abuse and Alcoholism, 2007)
Talking With Patients About Drug
Testing
Prior to testing, important tasks for the
practitioner are to explain to patients: (1) the
reasons for performing drug testing, (2) use
of the test results, and (3) the practitioner’s
duty to maintain condentiality. It should
also be explained to the patient that the
drug tests and the results will become
part of the patient’s record. Establishing a
trusting relationship in which patients feel
comfortable about conding substance use
helps address any questions or negative
reactions to testing or test results. If the
patient has language, hearing, or
vision-related challenges, accommodations
may need to be made with the use of a
translator or assist technologies. Key
practitioner actions that contribute to
such a relationship include:
• Communicating openly;
• Having an understanding attitude;
• Listening actively;
• Treating the patient with dignity
and respect;
• Reassuring the patient regarding
condentiality of medical records;
• Having a straightforward, but
nonjudgmental attitude; and
• Using a matter-of-fact, nonconfrontational
approach in explaining the reasons for
drug testing and any subsequent treatment.
Explicit consent for drug testing is not
required in primary care settings. However,
there are reasons why practitioners should
inform patients before drug testing:
• The practitioner–patient relationship.
Although patients may assume they will
be tested for cholesterol or glucose levels,
most do not expect to be tested for drug
use. Patients confronted with results
of tests that they did not realize were
being performed may feel betrayed by
the practitioner, possibly eliminating the
chance for discussion about substance
use problems and harming the
practitioner–patient relationship.
• Privacy. If the practitioner orders a test
and the cost is submitted to the insurance
company, the patient’s health insurance
company will know about it. Patients
should have the choice of deciding whether
they are willing to have their insurance
carrier learn this information.
• Reimbursement. Patients’ third-party
payers may not cover drug tests. If
insurance companies do not pay for the
test, patients should decide whether
they are willing to self-pay; this decision
should be made before the test is done.
The patient may want to pay out of pocket
to keep the drug test out of his or her
insurance record.
Before testing, the practitioner needs to
emphasize to patients the importance of
revealing all prescription and nonprescription
drugs (including OTC medications and herbal
preparations) they are taking. Patients may
not realize that OTC or herbal products can
affect drug test results.
39
Chapter 4—Drug Testing in Primary Care
Even if a patient refuses to consent to a
drug test, the conversation between the
practitioner and patient may facilitate a
discussion about possible substance use
problems. The practitioner could begin by
asking why the patient does not want to
have a drug test, or agree to re-visit the issue
during another visit. A patient may be willing
to examine his or her behavior after refusing
the test.
Discussing drug testing results can be
difcult. Patients need clear and thoughtful
explanations of the test results and the terms
positive, negative, adulterated, dilute, or
substituted. They need to understand why
the test was positive or negative and what
that means for the patient and any treatment.
All results should be presented in a
straightforward, nonjudgmental manner
using terms the patient understands.
Effective communication is essential for
the practitioner–patient relationship to be
successful in these circumstances.
Cultural Competency and Diversity
The ease or difculty in establishing and
maintaining a therapeutic alliance is affected
by many factors, including the amount
of time the practitioner can spend with
the patient, the backgrounds of both the
practitioner and the patient, the patient’s
ability to speak English, and acculturation
levels (if the patient is from another country).
Drug testing with some patients from diverse
groups can be challenging due to their
cultural beliefs, history, and heritage. Some
patients may distrust the medical profession
because of past abuses by the medical
community. They might feel additional shame
about SUDs because of the strong stigma in
their community, they might fear disclosure
to law enforcement, or they might possess
a different idea of what constitutes normal
drinking versus problematic drinking.
Some approaches to help improve
communication in these circumstances
include:
• Providing an explanation of the
practitioner’s perceptions of the problem
and listening, with sympathy and
understanding, to the patient’s perception
of the problem.
• Acknowledging and discussing the
differences and similarities in beliefs about
treatment.
• Recommending treatment and then
negotiating a treatment agreement (Berlin
& Fowkes, 1983).
Following are some ideas for the practitioner
to consider when treating patients from
diverse backgrounds:
• Culture is important in every patient’s
identity.
• Communication of cultural understanding
and respect is essential for establishing
rapport.
• Culture-related stresses and tensions can
induce illness.
• Culture-related behaviors or beliefs (e.g.,
religion, family structure and inuence,
health practices, traditional health
beliefs) affect patients’ acceptance of and
compliance with prescribed therapy.
• Nonverbal and verbal communication may
differ from culture to culture.
• Customs and attitudes surrounding SUDs
may differ from the accepted medical
denition.
• Awareness of prevailing cross-cultural
tensions and psychosocial issues may help
the practitioner understand patients from
that culture (Bobo, Womeodu, & Knox,
1991).
Clinical Drug Testing in Primary Care
40
Intercultural skills need to be as specic as
possible for each culture. For example, the
practitioner should:
• Attempt to understand how the patient’s
background and culture can affect
treatment.
• Elicit the patient’s understanding of drug
testing.
• Negotiate a culturally relevant care plan
with the patient as partner.
• Interpret verbal and nonverbal behaviors
in a culturally relevant manner.
• Acknowledge the patient’s role as an active
participant in his or her own care (Bobo et
al., 1991).
Monitoring Patients
Patients With an SUD
If the practitioner is providing substance
abuse treatment, drug testing can:
• Objectively monitor abstinence from drugs
or alcohol;
• Monitor response to treatment;
• Corroborate self-reports;
• Help address denials of substance use; and
• Identify relapse to substance use.
For example, an increasing number of
physicians provide medications for alcohol
use disorders (e.g., disulram, naltrexone).
Drug testing can be used to help monitor
patients’ use of drugs, if necessary, and
is needed before starting naltrexone. The
patient and practitioner need to negotiate
a plan of action to address the patient’s
substance use and monitor progress. Any
medical problem other than substance
use (e.g., hypertension) should also be
monitored, as should any abnormal biological
markers (e.g., elevated gamma-glutamyl
transpeptidase levels in patients who abuse
alcohol).
A practitioner using drug tests may seem
intrusive to some patients, whereas other
patients welcome the discipline imposed.
The practitioner and patient should
negotiate the use of any form of objective
monitoring beyond self-reports of substance
use. Biological monitoring should be viewed
as an informative measure, not cause for
punitive action against the patient. Repeated
positive urine drug test results mean that
the treatment plan is not working and that
another approach should be considered.
Efforts to reduce the patient’s substance use
by monitoring drug test results work best
in conjunction with open communication
between the practitioner and the patient.
Monitoring treatment compliance is a
trust issue, and trust is important for the
development of the therapeutic alliance. The
practitioner needs to create an environment
in which the patient feels safe to report
honestly how he or she is progressing in
recovery. Relapses are a normal part of the
natural history of recovery, and how the
practitioner responds to them is essential
to building a therapeutic alliance and trust.
Getting honest with oneself and others about
one’s substance use and its impact on one’s
life is essential to lasting recovery, so honesty
is an important ground rule for establishing
the patient–practitioner relationship. That
said, the practitioner should be clear early
on that addiction leads some patients to be
dishonest about their drug use, so a policy of
“trust yet verify” is used—drug testing and
corroboration from family can help verify
the patient’s reports. The practitioner should
express trust in the patient; then, if the
patient is not honest about reporting
substance use, the practitioner must address
the lack of honesty as a therapeutic issue that
impedes recovery. If a patient tries to deceive
the practitioner, the practitioner should be
direct yet empathic: “I know it is hard to stop
using. What do you think might help?”
The response to a positive drug screen in
patients being treated for an SUD depends
on more than one factor, including the types
of drugs found in the test. If positive results
41
Chapter 4—Drug Testing in Primary Care
continue and the patient is not progressing,
the patient may need referral to more
intensive treatment. However, if the patient
readily admits to a relapse and seems fully
committed to continuing treatment, the
practitioner should support the patient’s
recommitment to recovery. Each patient
needs to be assessed as an individual. If
the patient is receiving medication-assisted
treatment, the dosage may need to be
increased.
An important concept of substance abuse
treatment is that one failure (e.g., relapse,
leaving treatment), or even multiple
treatment failures, is not a reason to
deny further treatment to a patient. The
practitioner should expect relapses and be
prepared to respond in a therapeutically
appropriate manner. The patient may not be
able to achieve recovery after one, or even
several, treatment periods. SUDs are chronic,
relapsing conditions that often need repeated
interventions or treatments before a patient
is stabilized. The practitioner should not
expect that patients with problems related
to alcohol and drug use will have any less
difculty than other patients in making
signicant lifestyle changes.
Unless a practitioner is testing for all
substances (which is virtually impossible),
heavy reliance on drug tests can be
misleading in monitoring abstinence.
Patients can abstain from their substance
of choice while using other substances that
may not be part of a particular drug test
panel. Practitioners should test not only for
the patient’s substance of choice, but also
other commonly abused drugs. In general,
the practitioner should avoid using drug
testing as a punitive measure. A cooperative
practitioner–patient relationship includes
trusting the patient’s self-report of substance
use, with drug testing used to verify reports.
If a patient is currently in treatment for
substance abuse at a treatment center, he or
she is likely being tested for drug use. In this
case, it is cost effective—and in the patient’s
best interest—for the practitioner to ask the
treatment program (with permission from the
patient) for drug test results rather than to
repeat a drug test.
Monitoring Patients Receiving Opioids for
Chronic Noncancer Pain
Urine drug tests are becoming more common
to monitor patients receiving chronic opioid
analgesics. In pain management, drug tests
can be useful, but they need to be used
thoughtfully. The plan and reasoning for
drug testing for these patients needs to be
discussed thoroughly with the patient. Some
patients may nd drug tests intrusive; others
accept the practice. Drug tests tend to be
associated with drug abuse treatment and
some patients may be offended when asked
to participate in drug testing as part of pain
treatment.
Drug tests do not monitor therapeutic drug
levels; they provide information regarding
medication adherence to the prescribed
medication and/or the ingestion of illicit
drugs. The only exception is the use of serum
methadone levels. If the drug test shows
the use of illicit drugs in addition to the
prescribed medications, the patient needs to
be educated regarding the danger of using
illicit substances and opioid pain medications
and that substance abuse is not helpful to
long-term pain management. Some patients
may need to be referred to specialists in both
addiction and pain management.
To properly interpret urine drug screens, a
detailed understanding of the pharmacology
of the prescribed opioid and its relationship
to the urine-testing technique must be
understood by the prescribing provider. A
negative test result when a positive one
was expected (e.g., pain medication) may
also trigger patient resistance or feelings of
guilt, shame, or anger. In these cases, it is
important that the practitioner avoid arguing
with the patient and remain nonjudgmental.
For more information, see TIP 54: Managing
Chronic Pain in Adults With or in Recovery
From Substance Use Disorders (SAMHSA,
2012).
Clinical Drug Testing in Primary Care
42
Ensuring Confidentiality and 42
CFR Part 2
The concern about the adverse effects
that negative attitudes about SUDs
and discrimination have on patients in
recovery—and how those adverse effects
might deter people from entering
treatment—led the U.S. Congress to pass
legislation and the Department of Health
and Human Services (HHS) to issue a
set of regulations to protect information
about patients’ substance abuse. The law is
codied at 42 United States Code §290dd-
2. The implementing Federal regulations,
“Condentiality of Alcohol and Drug Abuse
Patient Records,” are contained in 42
CFR Part 2 (Vol. 42 of the Code of Federal
Regulations, Part 2). The law and regulations
severely restrict communications about
identiable patients by “programs” providing
substance use diagnosis, treatment, or
referral for treatment (42 CFR §2.11). These
rules are stricter than the general Health
Insurance Portability and Accountability Act
of 1996 (HIPAA) rules about disclosure of
personal health information. Under HIPAA,
information can be disclosed without written
consent for the purposes of routine clinical
care and most administrative functions.
Written permission from the patients for
these disclosures is generally required by 42
CFR Part 2.
In most primary care settings, 42 CFR Part
2 does not apply. Confusion persists about
whether general medical care settings (e.g.,
primary care clinics, hospital emergency
rooms) are subject to the law and related
regulations because they provide substance
abuse diagnosis, referral, and treatment as
part of their services. In 1995, HHS revised
the denition of the kinds of programs
subject to the regulations, clarifying that the
regulations do not usually apply to a general
medical care facility unless that facility (or
person) “holds itself out as providing, and
provides, alcohol or drug abuse diagnosis,
treatment or referral for treatment” (42 CFR
§2.11).
Practitioners should be aware that if a
healthcare practice includes someone whose
primary function is to provide substance
abuse assessment or treatment, and if the
practice benets from Federal assistance
(including Medicare or Medicaid payments),
that practice must comply with the 42 CFR
Part 2 law and regulations and implement
special rules for handling information about
patients who may have substance abuse
problems (CSAT, 1997). Clinicians who use a
controlled substance (e.g., benzodiazepines,
methadone, buprenorphine) for detoxication
or maintenance treatment of an SUD are
also subject to this regulation. However,
physicians who do not use a controlled
substance for treatment (e.g., naltrexone) are
not subject to the regulation (SAMHSA, n.d.).
In practices subject to 42 CFR Part 2, the
results of a patient’s drug test and substance
use history are condential and may not be
revealed to a third party without the patient’s
consent, except in certain circumstances (e.g.,
if the patient was mandated to treatment).
Patients must be told before being tested
whether the test results must be reported. In
addition, any releases of information must
specify that the information cannot be shared
with a third party without specic consent of
the patient.
Many States offer additional protection
to medical information about patients
that is as strict or stricter than 42 CFR
Part 2. However, each State has its own
set of rules, which means that the scope
of protection offered by State law varies.
Whether a laboratory test result is privileged
or protected information may depend upon
several factors:
• The type of professional holding the
information and whether he or she is
licensed or certied by the State;
• The context in which the information was
communicated;
• The context in which the information will
be or was disclosed; and
• Exceptions to any general rule protecting
information.
43
Chapter 4—Drug Testing in Primary Care
Which practitioners are covered depends on
the State within which the clinician practices.
Practitioners should consult with their
State medical or substance abuse treatment
authorities to ascertain the requirements and
regulations in their State. SAMHSA provides
a directory of State agencies for substance
abuse services located at http://www.samhsa.
gov/Grants/ssadirectory.pdf.
For more information, see Appendix B of TIP
24: A Guide to Substance Abuse Services for
Primary Care Clinicians (CSAT, 1997), and
Condentiality of Alcohol and Drug Abuse
Patient Records Regulation and the HIPAA
Privacy Rule: Implications for Alcohol and
Substance Abuse Programs (CSAT, 2005).
Preparing for Implementing Drug
Testing
Before starting a drug testing program, it is
recommended that the practitioner discuss
the needs of the program with the laboratory
toxicologist or other knowledgeable laboratory
staff. Some important areas to obtain
information about and to understand include:
• The strengths and limitations of the
different tests;
• Standard collection procedures;
• Possible cross-reactivities with the
targeted drugs that could affect test
results;
• Limitations of the tests offered by the
laboratory;
• Windows of detection for different
specimens;
• Conrmatory testing, which can be done
automatically, or only with specic request
of the practitioner;
• Cutoff levels and whether they are
appropriate for clinical purposes; and
• Cost of clinical drug test panels.
When ordering a laboratory test to detect
substances of abuse, practitioners and
staff need to order the correct test for the
substances of interest and complete the
required forms accurately. The practitioner
needs to know exactly what a test is—and is
not—measuring. For example:
• The specic drugs or metabolites that can
be detected by the test
• The cutoff concentration used by the
laboratory or the point-of-care test (POCT)
• The specic substance, class of substances,
cross-reacting drugs, and/or metabolites
that may yield a positive test result
• The drugs, drug classes, and/or their
metabolites for which the test is being done
• The drugs/drug classes that will not be
detected by the test
Collecting Specimens
No matter what the reason for drug
testing, collections of specimens have more
similarities than differences. As in workplace
drug testing, which has specic requirements
for collecting samples, clinical drug testing
should have established collection procedures
for that facility or ofce that follow the
College of American Pathologists, Clinical
Laboratory Improvement Amendments,
and local and State regulations. A properly
collected specimen is essential to a obtaining
an accurate test result, whether for a POCT
or for a test performed at a laboratory. The
person responsible for specimen collection
needs proper training. His or her duties
include:
• Establishing the identity of the patient;
• Explaining clearly the collection procedure
to the patient;
• Ensuring that the collection container is
appropriate for the specimen matrix;
• Labeling the specimen properly;
• Collecting a sufcient amount of the
specimen;
• Ensuring that the specimen collection
method prevents substitution, dilution, or
adulteration;
Clinical Drug Testing in Primary Care
• Preventing contamination from
environmental sources when collecting
specimens;
• Storing the specimen according to
the manufacturer’s or laboratory’s
recommendations (e.g., proper
temperature) to maintain specimen
integrity;
• Preventing loss of or tampering with
specimen by storing it in a secure area;
• Properly recording information; and
• Following universal precautions (e.g.,
wearing gloves and a mask, proper
disposal of contaminated materials).
Collection procedures for drug testing should
be conducted in ways that preserve patients’
dignity. The procedures should be written
and explained to patients before collection.
Product inserts should be the basis for
written protocols and not used as directions
when actually collecting and testing
specimens or reporting results.
The results of a drug test will not
provide a diagnosis of an SUD.
Conducting POCTs
Personnel assigned to conduct the POCTs
need to:
• Have access to current product inserts for
the laboratory collection device and for the
POCT device, if it is a combined collection
and testing device;
• Pay close attention to the instructions
provided with the test, particularly
regarding timing and reading the results
accurately;
• Understand possible cross-reactivities with
other substances, especially if they are
interpreting the results;
• Assay appropriate positive and negative
quality control samples;
• Decide under what circumstances
laboratory conrmatory tests will be
ordered; and
• Record test results according to the
protocols established by the practice.
If a practitioner is giving immediate
feedback to a patient—a major benet of
using POCTs— the practitioner needs to be
condent about what the test is measuring,
its results, and the limitations of the test.
POCT manufacturers generally have a
technical assistance telephone line to
answer questions. Chapter 5 provides details
about using urine drug tests for specic
drugs, including windows of detection,
cross-reactivities, limitations, and special
considerations for interpreting results.
Interpreting Drug Test Results
A drug test indicates whether a substance
or a prescribed medication is present at
levels below (negative) or above (positive)
the test cutoff concentration. A test result
can reveal that a specimen is negative,
positive, adulterated, substituted, or dilute.
Generally, drug testing cannot tell the
practitioner the amount of drug ingested by
the patient, whether a therapeutic level has
been achieved (e.g., opioids for pain relief),
or frequency of use, nor can it indicate the
patient’s level of intoxication, impairment, or
severity of abuse, when trying to determine
whether a patient may have an SUD. The
results of a drug test will not provide a
diagnosis of an SUD.
When interpreting drug test results, the
practitioner must know exactly what a test
is—and is not—measuring. The practitioner
must consider:
• The purpose of the drug test;
• The limitations of the test used;
• The drugs or drug metabolites being
detected and those not being detected;
• Potential cross-reactivities; and
• The limitations of the selected matrix.
44
45
Chapter 4—Drug Testing in Primary Care
Many other factors need to be considered
when interpreting drug test results (e.g.,
specic substance, class of substances,
cross-reacting drugs and/or metabolites that
may yield a positive result). Drug test results
may raise clinical concerns for practitioners,
or provide reassurance about patient
adherence to treatment. Testing may provide
unexpected information, but should never be
the sole basis for diagnosis and treatment
decisionmaking. Test results should be used
to supplement the information obtained
from a comprehensive patient interview, the
physical examination, and consideration of
the patient’s overall health.
To appropriately respond clinically, it
is important that there be thoughtful
consideration of drug test results, especially
those that seem unusual for a particular
patient or possibly incorrect. Other clinical
ndings must also be considered as well as
drug test results.
Result: Negative Specimen
A negative test result means that a particular
substance was not detected at or above the
cutoff concentration in the specimen. A
negative screening test result is rarely
followed by a conrmatory test, but can
be done if requested by the practitioner.
Laboratories perform conrmatory tests
on positive results, either routinely or only
for certain drug/drug class positives (e.g.,
amphetamines, opiates) (White & Black,
2007), depending on the laboratory. It is
imperative that the clinician is familiar with
the laboratory’s practices and procedures for
testing.
The practitioner’s response to a negative drug
test result is based on the patient’s diagnosis
and reason for testing:
• If the patient is being treated for an SUD,
consistently negative results—along with
improvement in other areas of the person’s
life—may warrant a change in level of
treatment (e.g., decreased frequency
of visits, decreased testing frequency,
changing from observed to nonobserved
urine collection).
• If the patient is being prescribed
medications with addictive potential (e.g.,
opioids, sedatives), a negative drug test
warrants a reassessment that may lead
to more frequent drug testing and ofce
visits.
A negative drug test does not necessarily
mean the patient has not used a particular
substance or taken the prescribed medication.
Negative test results can occur if:
• Errors were made in interpretation of the
test.
• The patient has induced enzyme levels
from smoking or liver disease and
eliminates the medication more rapidly
than usual (e.g., methadone).
• The patient has a shortened
gastrointestinal tract from surgery and
does not absorb the drug sufciently for
detection.
• The patient ran out of medication.
• The patient took the medication but not
when expected or during the window of
detection for the ordered test.
• The patient was thirsty and drank
sufcient water to dilute the specimen.
• The patient may have consumed an
excessive amount of uids to deliberately
dilute a urine specimen.
• The appropriate test for a particular
medication or substance was not
performed.
• The cutoff concentration used in the test
was set too high, so small amounts of the
drug/drug metabolites were missed.
• The parent drug and/or its metabolites
were excreted before specimen collection
(e.g., outside the detection window).
• The specimen may have been adulterated
or substituted.
Clinical Drug Testing in Primary Care
46
If a negative conrmatory test result is a
surprise based on the patient’s self-report,
collateral report (e.g., from a spouse or
partner, from a parent stating that he or
she has found drugs or drug paraphernalia
in a child’s room), or other evidence, the
practitioner should reconsider the testing
procedures and assessing the patient’s
behavior. The practitioner could contact
the laboratory and discuss the results with
laboratory personnel, especially to see
whether the negative report came from
values that were just below the laboratory’s
cutoff concentration. Repeated urine testing
could be done, or oral uid could be tested.
The practitioner could also consider:
• Changing or including additional drugs for
which testing is performed based on the
information received.
• Adding specimen validity testing or testing
the original negative specimen for validity.
• Changing the matrix tested (e.g., test urine
instead of oral uid for a longer detection
window), if possible (e.g., based on drug
detection period, sensitivity, ease of
adulteration/substitution of the specimen).
• Testing repeated serial urines.
• Changing the drug-testing methods (i.e.,
change from POCT to laboratory test).
• Determining whether the testing occurred
outside of the detectable window for the
substance.
A conrmed negative test result for a patient
receiving a prescribed medication, such
as in pain treatment, is of concern. Again,
the practitioner should rst check with the
laboratory about the validity of the test:
Was the cutoff concentration low enough to
measure therapeutic levels of the medication?
In this case, retesting may be appropriate.
Was the correct test performed to detect the
prescribed substance (e.g., oxycodone is not
detected in a standard 5-drug panel)?
If the negative test result is valid for
prescribed scheduled medications, the
practitioner must decide how to proceed with
the patient who is, at best, not adhering to
his or her prescribed medication regimen
or, at worst, diverting the medication. For
many reasons, a negative test should not
be used to blame the patient for “diversion”
unless there is other credible, incriminating
information (e.g., witnessed attempts to sell
the medication, drug-seeking documentation
from prescription monitoring programs).
Result: Positive Specimen
A positive screening test result means that a
particular substance was detected at or above
the administrative cutoff concentration in the
specimen. Conrmatory tests are frequently
performed for specimens with positive
screening results. If the patient admits drug
use when informed of positive results from a
POCT, a conrmatory test is not needed.
False-positive results are possible with
screening (initial) tests. If a presumptive
positive is conrmed by a second methodology,
such as gas chromatography/mass spectrometry
(GC/MS) or liquid chromatography/mass
spectrometry/mass spectrometry (LC/MS/
MS), a false positive is highly unlikely if the
test is performed correctly. If a positive result
is surprising and the patient vehemently
denies recent or current use, the practitioner
should order a laboratory conrmatory
test if such a test is not already part of the
laboratory’s testing agreement.
Interpretation of positive tests can sometimes
be complex, especially if a patient is being
monitored for abstinence following heavy
drug use. With frequent use, signicant bodily
accumulation of drugs can occur with the
consequence that drug metabolite(s) may
be excreted for extended periods. This is
especially true for highly lipid soluble drugs,
such as marijuana (tetrahydrocannabinol)
and phencyclidine, but it also applies to other
drugs, such as cocaine and heroin. A patient
who is recently abstinent may continue to test
positive for days to weeks depending upon
the drug and pattern of use. Distinguishing
this normal pattern of body elimination of
47
Chapter 4—Drug Testing in Primary Care
drugs from new drug use can be difcult.
Huestis and Cone (1998) have published
methods for evaluating creatinine-normalized
cannabinoid urine results between two
specimens collected at least 24 hours apart
to predict new marijuana use. These models
were more recently updated and improved to
take into account the specic times between
two urine collections (Smith, Barnes, &
Huestis, 2009). In a similar vein, Preston,
Silverman, Schuster, and Cone (1997)
developed a model for differentiating new
cocaine use from residual cocaine metabolite
excretion during abstinence. These criteria
are based on established pharmacokinetics of
benzoylecgonine and include urine creatinine
normalization for control of variations in
water intake and excretion.
If the conrmatory test result is positive for
nonprescribed substances, the practitioner
should review the patient’s use of prescribed
medications, OTC products, and herbal
products to determine whether any of these
may be the source of the positive result (e.g.,
poppy seeds causing a positive for codeine or
morphine; high doses of morphine causing a
positive for hydromorphone). The practitioner
may also retest using a different matrix.
However, it is worth noting that changing
matrices makes interpretation difcult. Hair
provides a longer detection window than do
other matrices. If a hair specimen was used
for testing, a patient could test positive for
drug use, even if he or she has not used the
substance for weeks. Segmenting a hair
specimen is useful to narrow the window in
which a positive is observed. However, hair
testing is expensive. A urine or oral uid
drug test could provide a more accurate
picture of very recent use. However, if the
second specimen using the same or a different
matrix is negative, it does not refute the
scientic validity of the rst test.
Clearly, drug test results should never be the
sole criteria used for diagnosis of an SUD or
making treatment decisions. The practitioner
should not take action based solely on drug
test results, but should consider them along
with behavioral and physical assessments
and any collateral information obtained (with
permission of the patient) from a spouse,
partner, or family member.
Other possible changes in drug-testing
procedures include:
• Increasing the testing frequency to
discourage illicit drug use by the patient,
or possible diversion of prescribed
medications;
• Changing the drugs tested for (e.g., test for
another class of drugs) to detect the full
scope of the patient’s drug use; and
• Changing the drug-testing methods (e.g.,
use a laboratory test instead of a POCT or
request a conrmatory test for all initial
tests) to rule out false-positive results.
Other changes to treatment are discussed
in the section on monitoring patients in
Chapter 4.
Result: Adulterated or Substituted
Specimen
Urine is the easiest specimen to adulterate,
and commercial formulas of synthetic urine
are available for substitution. Other uids,
including water, also have been used for
substitution. If the test result indicates
that the specimen has been adulterated
or substituted, the practitioner collects
another specimen and reviews procedures to
determine whether the temperature and pH
of specimens are being checked immediately
after collection. For patients who seem to
have several test results of adulterated
or substituted urine, stricter collection
procedures could be instituted for that
patient. These could include:
• Ensuring that adulterants, such as
soap, ammonia, or bleach are not readily
available in the collection area when that
patient provides specimens;
• Prohibiting personal belongings in the
bathroom;
Clinical Drug Testing in Primary Care
48
• Turning off the source of running water
during collection and putting blue dye in
the toilet; and
• Observing specimen collection.
The practitioner should review the patient’s
history, interview the patient, and observe
the patient’s behavior during the interview.
The patient may need to be referred to a
more intensive level of care. The drug-testing
program can also be modied by adding
a specimen validity test to the POCT or
laboratory test, and changing the specimen
matrix (e.g., oral uid is least likely to be
adulterated).
Result: Dilute Specimen
A dilute urine specimen can be negative
or positive, depending upon the degree of
dilution and amount of drug excreted. If the
test result shows that the specimen has been
diluted, the practitioner should discuss both
the dilution and the negative or positive
test result with the patient. In addition, the
practitioner could:
• Test a different matrix, if possible;
• Collect and test a new specimen;
• Review the specimen collection site and
ensure that bluing has been added to the
toilet, that the water is turned off to the
taps, and that patients are not allowed to
take personal effects into the bathroom; or
• Consider medical reasons for diluted
urine (e.g., conditions, such as routinely
receiving diuretics, resulting in polyuria).
Result: Invalid Urine Specimen
An invalid result is one in which scientically
supportable analytical test results cannot
be established for a specimen. An invalid
laboratory test result for urine can be caused
by many factors, such as:
• A physiological inconsistency between
the patient’s urine creatinine and specic
gravity;
• An interference in the screening or initial
test analysis;
• An interference in the conrmatory assay;
• The presence of oxidizing compounds at or
above a cutoff set by the laboratory;
• A urine pH greater than or equal to 3.0 but
less than 4.5 or outside other range set by
the laboratory or POCT manufacturer;
• A urine pH greater than or equal to
9.0, but less than 11.0 or outside other
range set by the laboratory or POCT
manufacturer;
• The presence of nitrites in urine at or
greater than 200 μg/mL but less than
500 μg/mL, or above a level set by the
laboratory or POCT manufacturer;
• The possible presence of chromium (VI);
• The possible presence of a halogen (e.g.,
bleach, iodine, uoride);
• The possible presence of surfactant (e.g.,
soap);
• The physical appearance of a specimen
is such that the laboratory feels analysis
of the specimen might damage its
instruments; and
• Other factors determined by the laboratory
for an invalid specimen.
An invalid test result is not denitive proof
of specimen tampering. The practitioner
should consider other possible causes before
assuming that the patient has attempted to
subvert the test. The practitioner could try to
determine the reason for the report or discuss
possible causes with the laboratory (e.g.,
Was an unidentied adulterant suspected?
Were the specimen’s physical characteristics
inconsistent with human urine?). A review
of the patient’s history may reveal a medical
explanation (e.g., a medication that could
have interfered with the test).
The practitioner could also have another
specimen collected and tested and ensure
that the collector follows proper procedures,
including restricting patient access to
49
Chapter 4—Drug Testing in Primary Care
materials that could be used to adulterate or
substitute the specimen.
Results are also reported as indeterminate or
inconclusive. The practitioner should consider
the possible causes, including storage and
transport irregularities, and potential
medical explanations (e.g., a medication
that could have interfered with the test).
If this happens often, the practitioner may
want to ask the patient to return for further
discussion and repeat the test.
Frequency of Testing
Drug testing can be done when conducting an
assessment when an SUD is suspected, or as
a baseline when prescribing medications with
addictive potential. The subsequent frequency
of drug testing depends on the practitioner,
the individual patient, the diagnosis, and the
reason for drug testing.
In opioid pain management, testing can
be done both to ensure compliance with
prescribed medications and to identify abuse
of illicit substances. Drugs of interest in
this instance include benzodiazepines and
opioids (e.g., oxycodone, methadone, fentanyl,
hydrocodone, hydromorphone, morphine).
Drug tests can be done before providing
initial prescriptions or rells (White &
Black, 2007) or for other medications with
addictive potential. Testing can also be done
if the patient exhibits aberrant behavior,
if diversion of prescribed medications is
suspected, or randomly to monitor treatment.
For the patient being treated for an SUD,
drug tests can be done:
• With changing frequency as the patient
progresses (less often as the patient
progresses, or more often with lack of
progress);
• If relapse is suspected;
• If the patient exhibits aberrant behavior;
or
• Randomly to monitor treatment.
For the patients receiving medications,
particularly opioids, with abuse potential,
drug tests can be done during every visit,
randomly, before providing prescription
rells, or if the patient exhibits aberrant
behavior. The frequency can also change with
several drug tests that show that the patient
is taking the medication as prescribed and is
not positive for illicit drugs.
A drug test may not be needed if the
patient admits illicit drug use or treatment
noncompliance for prescribed medications
when coming to his or her appointment.
Documentation and
Reimbursement
Proper documentation is needed for both patient
record keeping and to obtain reimbursement.
Documentation
In addition to keeping accurate patient
medical records, practitioners must ensure
proper documentation of the use of POCTs.
This includes (Howerton et al., 2005):
• Written procedures for performing POCTs;
• Inventory control—lot numbers and
expiration dates for POCTs;
• Documentation of staff training and
reassessment;
• Quality assurance test results;
• Documentation of problems and problem
resolution; and
• Copies of laboratory test orders and
results.
Patient medical records should document:
• The medical necessity for drug testing;
• Tests performed and test results;
• Changes made to the treatment plan based
on test results; and
• Referrals made.
Clinical Drug Testing in Primary Care
50
Reimbursement
Testing for alcohol or drugs is billed by the
specic biological tests conducted according
to the Current Procedural Terminology (CPT)
codebook (American Medical Association, 2006).
Insurance coverage for alcohol or drug testing
varies by carrier. Careful documentation of
the need for testing assists with obtaining
reimbursement. The current issue of the CPT
codebook should be consulted to obtain proper
reimbursement.
Some CPT codes that are used for testing
include:
• 80100: For qualitative screening tests used
to detect the presence of multiple drug
classes.
• 80101: For qualitative screening tests used
to detect the presence of one drug class.
• 80102: For each conrmatory test.
• 82055: Alcohol testing (any method other
than breath).
• 82075: Alcohol testing (breath).
Centers for Medicare & Medicaid Services
uses different codes:
• G0430-QW: When multiple drug classes
are tested and the testing methodology
does not use the chromatographic method
• 80100-QW: When testing for multiple drug
classes that do use the chromatographic
method
• G0431: Used, per drug class, when
performing a test for a single drug class
The medical necessity for testing can
be documented by using International
Classication of Diseases codes (i.e., harmful
use or dependence syndrome) from the
International Statistical Classication of
Diseases and Related Health Problems,
Volume 1: 10th Revision (World Health
Organization, 1992). However, the patient
may want to pay for a drug test and not
submit the cost to the health insurance
company. This should be discussed with the
patient.
51
Chapter 5—Urine Drug Testing for Specific
Substances
In This Chapter
• Window of Detection
• Specimen Collection
• Adulteration,
Substitution, and
Dilution
• Cross-Reactivity
• Alcohol
• Amphetamines
• Barbiturates
• Benzodiazepines
• Cocaine
• Marijuana/Cannabis
• Opioids
• Other Substances of
Abuse
Urine is the most rigorously evaluated and most commonly
used matrix for drug testing (Watson et al., 2006). All results
are affected by laboratory test or point-of-care test (POCT)
cutoff concentrations. Therefore, practitioners should always
consult with laboratory staff when ordering laboratory tests
or carefully read POCT package inserts before using the test.
Numerous POCTs are available for urine drug testing.
Window of Detection
The window of detection for urine falls in the intermediate
range, compared with the detection period or window for other
matrices. Many factors inuence the window of detection
for a substance. Factors include, but are not limited to, the
frequency of use (chronic or acute), amount taken, rate at
which the substance is metabolized, cutoff concentration of
the test, patient’s physical condition and, in many cases, body
fat. Some hepatic, renal, endocrine, and other pathologies
may extend the detection window.
Drugs are present in urine from within minutes of use to
several days after, depending on the substance; quantity
ingested; the degree to which the bladder was lled with
drug-free urine at the start of drug use; the patient’s hepatic,
cardiac, and renal function; the patient’s state of hydration;
and drug type. Drugs that are smoked or injected are detectable
in urine samples almost immediately. Detection rates for drugs
taken orally are slower, taking up to several hours and
peaking at about 6 hours (Dolan et al., 2004).
The window-of-detection estimates used in this chapter
are from several sources: Cone (1997), Dasgupta (2008),
Verstraete (2004), Warner (2003), White and Black (2007),
Wolff et al. (1999), and Wong and Tse (2005).
Many urine drug tests detect the drug metabolite, rather
than the drug itself. As a general rule, drug metabolites
remain in the body for a longer period than does the parent
drug, allowing for a longer detection period. For example,
when the test is for cocaine using urine, the target compound
is usually the metabolite, benzoylecgonine, rather than the
parent cocaine molecule.
Clinical Drug Testing in Primary Care
5252
It may be difcult to detect illegal substances
in urine specimens of patients who stop use
for several days before providing a specimen.
Most substances of abuse are detectable in
urine for approximately 2–4 days (Center for
Substance Abuse Treatment [CSAT], 2006b;
Cone, 1997). However, the detection time may
be prolonged when large, frequent doses are
taken over a long period (CSAT, 2006b). For
example, one dose of intranasal cocaine may
be detectable in urine for 3–5 days using
a cutoff of 300 ng/mL after ingestion, but
daily, heavy cocaine use may be detected for
additional days following discontinuation
of use (Verstraete, 2004). Chronic use of
marijuana may be detectable for up to 30
days after use is stopped.
Specimen Collection
Urine collection usually is easier than
collecting blood, and samples are available in
sufcient quantities (Warner, 2003). Urine
sample collection is not usually observed in
primary care settings. Clinical drug testing
usually does not warrant direct observation
that may be necessary in forensic or substance
abuse treatment program testing. However,
if it is suspected that a patient is tampering,
diluting, or adulterating urine specimens,
some measures used in forensic or workplace
testing can be used to prevent this, including:
• Directly observing specimen provision;
• Turning the water off to the taps and
adding a bluing agent to the toilet tank to
avoid sample dilution;
• Not providing hand soap in the restroom
where the sample is being done;
• Not storing cleaning agents in the
restroom (e.g., ammonia-containing
products, bleach, toilet cleaning products);
and
• Not allowing coats, purses, or bags into the
restroom with the patient.
Patients who exhibit “shy bladder syndrome”
(inability to void) may need to consume
liquids to provide a specimen (e.g., 8 oz. of
water every 30 minutes, but not to exceed a
maximum of 40 oz. over a period of 3 hours,
or until the patient has provided a sufcient
urine specimen).
Once the specimen is collected and labeled:
• The appearance and color of the urine
sample should be documented.
• The use of primary collection containers
with a temperature-sensitive strip on
the outside is recommended, rather than
placing a thermometer or temperature
strip into the urine.
• The urine specimen temperature should be
recorded within 4 minutes of collection; the
temperature should be between 90°F and
100°F.
Additional clinical testing, such as a routine
urinalysis (e.g., pH and tests to detect
the presence of oxidizing components and
adulterants) can be conducted on an aliquot
separate from that used for urine drug testing
to avoid any argument that a positive was the
result of a foreign object being placed in the
patient’s urine specimen.
Adulteration, Substitution, and
Dilution
Urine tests can be reported as adulterated,
substituted, or dilute.
Adulteration
An adulterated urine specimen is one
containing a substance that is not normally
found in urine or that is normally found,
but is in abnormal concentrations. In vitro
adulterants are foreign substances added to
the urine specimen after voiding. Adulterants
work by interfering with immunoassay and/
or conrmatory assay function, or they
convert the target drug to compounds not
Chapter 5—Urine Drug Testing for Specic Substances
5353
detected by the test (Jaffee, Trucco, Levy, &
Weiss, 2007). Ordinary household products
(e.g., laundry bleach, toilet bowl cleaner,
hand soap, vinegar, ammonia, eye drops)
have been used for many years to adulterate
urine specimens to obtain a negative drug
test result (Dasgupta, 2007). Household
products that alter the pH of urine to a value
outside the physiologic range can be easily
detected by determining the pH of the sample
(Dasgupta, 2007). Products such as bleach
and other oxidizing agents can be detected
with a general oxidants assay.
Numerous types of commercial adulterants
are available via the Internet. The following
list is a summary of such products by active
ingredient (Jaffee et al., 2007):
• Glutaraldehyde (e.g., “Clean X”) can
interfere with absorbance rates on
immunoassay tests, masking the presence
of substances such as the marijuana
metabolite, 11-nor-9-carboxy-THC
(THCCOOH), opioids, cocaine metabolites,
morphine, amphetamine, phencyclidine
(PCP), and most other immunoassay
tests. The presence of glutaraldehyde
usually is detected by observing abnormal
immunoassay results; however, other
substances can also cause an abnormal
immunoassay result.
• Sodium or potassium nitrite (e.g., “Klear,”
“Whizzies”) can mask the presence of
marijuana metabolite in immunoassay
tests and the presence of THCCOOH in
conrmatory tests. Abnormal nitrites in
urine can be detected by a specic nitrites
assay or in a general oxidants assay.
• Pyridinium chlorochromate (PCC,
commercially known as “Urine Luck”)
is an oxidizing agent that masks the
presence of THCCOOH and, depending
on the pH of the urine, can affect test
results for morphine. Cocaine metabolites,
amphetamine, and PCP are not affected
by PCC (Dasgupta, 2007). Chlorochromate
and other oxidizers, such as dichromate,
can be detected in urine using a general
oxidants assay.
• Peroxide/peroxidase (e.g., “Stealth”) can
oxidize drugs and their metabolites,
making THCCOOH and lysergic acid
diethylamide (LSD) undetectable by
immunoassay tests. The peroxide/
peroxidase combination may be difcult
to detect in urine that is not fresh because
both hydrogen peroxide and peroxidase
tend to degrade with time.
The effectiveness of an adulterant depends on
the amount of the adulterant added and, in
some instances, the concentration of the drug
in the sample. Specimen validity tests can
detect many adulterants in addition to those
described above.
Substitution
Synthetic urine products can be submitted
when collection of a urine specimen is not
observed. These products are premixed
liquids with the characteristics of natural
urine (i.e., correct pH, specic gravity, and
creatinine levels). To achieve the temperature
of recently voided urine, synthetic urine
products can be heated in a microwave or
taped next to a heating pad in a pocket.
Sometimes, another person’s urine is
submitted.
More commonly, water or a saline solution is
substituted for urine. Thus, a urine specimen
is considered substituted when the creatinine
concentration on both the initial and the
conrmatory tests is less than 2.0 mg/dL
and the specic gravity is less than or equal
to 1.0010 or greater than or equal to 1.0200
(Substance Abuse and Mental Health Service
Administration [SAMHSA], 2010b).
Dilute Specimens
Diluting the urine sample to the point
where the targeted drug is below the cutoff
concentration is another way to obtain a
negative test result. For instance, consuming
water in more-than-normal quantity and
taking diuretics can dilute the urine sample.
Individuals may also add water from the
tap or toilet bowl to dilute specimens if tap
Clinical Drug Testing in Primary Care
5454
water is available in the restroom and/or
bluing has not been added to the commode
water. Commercial products are available
that promise to “cleanse the urine.” These
products advocate consuming large amounts
of tea or other uids, increasing urine volume,
thereby diluting drugs in the urine. Reducing
the amount of time between notice that a
specimen will be collected and the time of
collection reduces the potential for the patient
to consume enough uids to dilute the urine.
A laboratory will report a urine specimen
as dilute in conjunction with a positive or
negative drug test when the creatinine
concentration is greater than or equal to
2 mg/dL and less than 20 mg/dL, and the
specic gravity is greater than 1.0010
and less than 1.0030 (SAMHSA, 2010b).
Dilution may raise suspicion of tampering,
but does not necessarily conrm tampering.
Other factors need to be considered, such
as whether the patient is taking a diuretic,
eating a strict vegetarian diet, or maintaining
a high state of hydration. Other factors
include whether the patient was working
in hot weather conditions and drank large
amounts of uid or drank uids immediately
before providing the specimen.
Cross-Reactivity
The cross-reactivity of urine immunoassay
tests varies by drug class. For example,
tests for cocaine measuring its principal
metabolite, benzoylecgonine, have low cross-
reactivity with other substances. However,
tests for amphetamine/methamphetamine
usually are extremely cross-reactive, and
further laboratory testing using a method
different in principle from immunoassay
(i.e., not a second immunoassay) is required
to conrm amphetamine use (Gourlay et
al., 2010). As stated above, cross-reactivity
is many times viewed as a negative aspect
of immunoassay. However, cross-reactivity
does have a positive side. An immunoassay
that is specic for morphine will detect only
morphine and will miss other opiates (e.g.,
hydrocodone) that a patient might be using
without the treating physician’s knowledge.
Thus, a general opiates screen is preferred
over a specic test when looking for
opiate-type drugs. Lack of cross-reactivity
also may affect testing, such as that
performed for oxycodone, as discussed
under “opioids.”
Alcohol
The window of detection for alcohol is 7–12
hours. The frequency of alcohol use minimally
affects the window of detection; however,
ingestion of large amounts results in a longer
detection time in body uids than ingestion
of a small amount of alcohol. The metabolism
of ethanol may be accelerated in people who
use chronically or binge. Approximately
90–95 percent of alcohol is oxidized in the
liver before elimination in the urine, and
only 1–2 percent of ingested alcohol is
excreted unchanged in the urine (Moeller,
Lee, & Kissack, 2008). Because of this rapid
metabolization, blood tests or the standard
hand-held breath devices (breathalyzers)
are often used, and in clinical settings, urine
alcohol tests are used far less frequently than
are blood tests.
Urine can be analyzed for alcohol through
chemical assays, enzyme immunoassays, or
gas-liquid chromatography (GLC), with the
most accurate reading produced by GLC.
Urine drug tests for alcohol indicate only
recent ingestion; they cannot identify long-
term abuse. Furthermore, a urine ethanol
can show use prior to the collection of the
urine specimen only within a reasonable
timeframe. Alcohol in blood or a blood product
(e.g., serum, plasma) or a breath alcohol is
required to show impairment and the degree
of impairment.
Biomarkers, such as the gamma-glutamyl-
peptidase, carbohydrate-decient transferrin,
aspartate amino transferase (measured in
serum), and erythrocyte mean cell volume
tests may conrm a suspicion of long-term
alcohol abuse or dependence. Ethyl glucuronide
EtG) and ethyl sulfate are direct metabolites
Chapter 5—Urine Drug Testing for Specic Substances
5555
of ethanol that can be measured in urine.
Testing for EtG is becoming more common to
monitor alcohol consumption for people who
have been ordered to abstain. However, more
research is needed to establish standards
to rule out possible exposure to alcohol in
commercial products, such as mouthwash and
hand sanitizers, versus drinking of alcoholic
beverages (CSAT, 2006a). More information
about biomarkers for alcohol use disorders is
in The Role of Biomarkers in the Treatment of
Alcohol Use Disorders, 2012 Revision.
Amphetamines
The SAMHSA workplace cutoff concentration
for amphetamines is 500 ng/mL for initial
testing, and 250 ng/mL for conrmatory
testing. To be reported positive for
methamphetamine, a specimen must also
contain amphetamine at a concentration
equal to or greater than 100 ng/mL
(SAMHSA, 2008).
The window of detection varies. A single dose
of amphetamine or methamphetamine can
be detected in the urine for approximately
24 hours, depending upon urine pH and
individual metabolic differences. People
who use chronically and at high doses may
continue to have positive urine specimens for
2–4 days after last use (SAMHSA, 2010b).
Methylenedioxyamphetamine (MDA),
methylenedioxymethamphetamine (MDMA),
and methylenedioxyethylamphetamine
(MDEA) can be detected for 1–2 days (Moeller
et al., 2008; SAMHSA, 2010b).
Drug tests for the presence of amphetamine
are among the hardest to interpret.
Methamphetamine is the target analyte for
amphetamine/methamphetamine testing.
Immunoassay tests are highly cross-reactive
and may detect other sympathomimetic
amines, such as pseudoephedrine, readily
available as over-the-counter (OTC)
products. Structural similarities of many
OTC products—including diet agents;
decongestants; and several prescription
medications, such as those to treat attention
decit/hyperactivity disorder, narcolepsy,
and Parkinson’s disease, or to suppress
appetite—can cause initial positive test
results. Adderall is an amphetamine and will
result in a positive test for amphetamine.
Methamphetamine exists as two optical
isomers (stereoisomers) that are designated
d- and l-. The d-form has high abuse
potential. The l-form in therapeutic doses
has a primarily peripheral action and is
found in some OTC products (Kwong, 2008a,
2008b). Immunoassay tests for amphetamine
and methamphetamine can be divided
into two types: (1) those designed to detect
amphetamine and methamphetamine, only;
and (2) those that also have variable
cross-reactivities with “designer
amphetamines,” such as MDA, MDMA, and
MDEA, as well as with sympathomimetic
amines (e.g., ephedrine, phentermine,
pseudoephedrine, phenylpropanolamine)
(Kwong, 2008a, 2008b).
Typical immunoassay tests do not distinguish
methamphetamine and/or amphetamine
use from use of OTC products containing
sympathomimetic amines. All presumptively
positive urine “amphetamines” results should
be conrmed by an alternate methodology
different in principle from the immunoassay
used to produce the screening result (White
& Black, 2007). A conrmed test by gas
chromatography/mass spectrometry (GC/MS)
for methamphetamine can either be
d-methamphetamine (licit or illicit) or
OTC nasal spray. A conrmed test for
methamphetamine is insufcient to
distinguish illicit drug use from use of an
OTC product. A separate test is available
that is offered by most laboratories that
distinguishes illicit methamphetamine
(d-methamphetamine) from OTC nasal
inhaler (l-methamphetamine). This
specialized conrmatory test, stereospecic
chromatography, is necessary to distinguish
methamphetamine, amphetamine, and their
isomers from legitimate sympathomimetic
agents (Gourlay et al., 2010). However, a
result conrmed by a second methodology,
such as GC/MS, is denitively amphetamine
Clinical Drug Testing in Primary Care
5656
and/or methamphetamine. Cross-reactivity
with MDMA, MDA, and/or MDEA is benecial
in that, once conrmed by an alternate
methodology, it may uncover a previously
unsuspected substance abuse problem.
Patients should be advised to avoid the use
of this type of OTC nasal spray when being
tested. A conrmed test for amphetamines
or methamphetamines can occur because a
number of other prescription medications
metabolize to these isomers. The patient
needs to be questioned regarding the reasons
for taking the medication to determine
whether it is by prescription or is being
misused.
Tests for amphetamine cross-react with
several other substances and are too
numerous to present a comprehensive
list. A conrmed test for amphetamine or
methamphetamine can occur because a
number of other medications metabolize
to these. The product inserts should be
consulted for the current list of cross-reacting
drugs. Substances known to metabolize to
methamphetamine and amphetamine include
benzphetamine, dimethylamphetamine,
famprofazone, fencamine, furfenorex, and
selegiline (SAMHSA, 2010b). Substances
known to metabolize to amphetamine
include amphetaminil, clobenzorex,
ethylamphetamine, fenethylline, fenproporex,
mefenorex, mesocarb, and prenylamine
(SAMHSA, 2010b).
Barbiturates
The incidence of barbiturate abuse is low
compared with abuse of other drugs or
alcohol (SAMHSA, 2009). Barbiturates (sans
phenobarbital) are detected easily using a
variety of immunoassays, even though only
a small amount of the parent drug is found
in the urine. The use of barbiturates may
be conrmed readily using several different
methods including, but is not limited
to, GC/MS and liquid chromatography/
tandem mass spectrometry (LC/MS/MS)
due primarily to the high doses commonly
administered or taken (Levine, 2010). Most
urine immunoassay tests use secobarbital as
the calibrator, at a cutoff concentration of 200
ng/mL or 300 ng/mL. Cross-reactivity with
other barbiturates varies with this assay,
and the detection window is dose dependent.
Several commonly used assays generally
cross-react with and detect butabarbital and
amobarbital (Kwong, 2008b). The window of
detection depends on the type of barbiturate
(see Exhibit 5-1).
Exhibit 5-1. Barbiturates—Window of Detection
Selected Barbiturates Window of Detection
Short acting (e.g., pentobarbital, secobarbital) 4–6 days after the last use (cutoff of 300 ng/ml)
Intermediate acting (e.g., amobarbital, butabarbital) 3–8 days (cutoff of 300 ng/mL)
Long acting (e.g., phenobarbital) 10–30 days (cutoff of 300 ng/mL)
Sources: Baselt (2008); White & Black (2007).
Benzodiazepines
The results of urine drug tests for
benzodiazepines may be challenging to
interpret without a basic knowledge of
the pharmacokinetics of the different
benzodiazepines. Like barbiturates,
benzodiazepines are classied by their
elimination half-lives. It is important to
know a test’s sensitivity and specicity
for the benzodiazepine in question.
False-negative results can occur if a test
is set to detect only one benzodiazepine or
its primary metabolite(s), and the clinician
is trying to monitor a non-cross-reacting
benzodiazepine. Because the parent drug
in the benzodiazepine class is usually
undetectable in urine drug tests,
drug-screening immunoassay tests are
usually designed to detect a specic metabolite,
57
Chapter 5—Urine Drug Testing for Specic Substances
57
either unconjugated oxazepam or its
glucuronide conjugates. Immunoassay tests
are more likely to detect benzodiazepines that
are metabolized to the targeted compound
and may miss the other non-cross-reacting
compounds.
Benzodiazepines can be divided into several
groups, based on their metabolites:
• Some benzodiazepines (e.g.,
chlordiazepoxide, diazepam, temazepam)
are metabolized to oxazepam. Oxazepam
is conjugated into an inactive glucuronide
metabolite.
• Nitrobenzodiazepines (e.g., clonazepam
which is primarily reduced to
7-aminoclonazepam, which is further
metabolized) are usually reduced to the
corresponding amino compound, but
are not converted into oxazepam or its
conjugate.
• The triazolobenzodiazepines such
alorazepam, estazolam, and triazolam
tend to form hydroxyl derivatives that are
separate and distinct from oxazepam.
• Other benzodiazepines (e.g., lorazepam,
urazepam) have a unique metabolism
that does not result in the formation of
oxazepam.
Clinical laboratories usually use cutoff
concentrations of 200 ng/mL or 300 ng/mL,
which can detect use of a benzodiazepine, but
may not necessarily detect a low therapeutic
dose (e.g., triazolam) (Warner, 2003).
Flunitrazepam (Rohypnol), commonly known
as “Rooes,” is a Schedule I substance.
Flunitrazepam is one of the so-called “date-
rape” drugs and shows good to excellent
cross-reactivity in most commercial urine
benzodiazepine assays except the Neogen,
Immunalysis, and Randox assays. If ingested,
unitrazepam and/or its metabolites may
be detected for approximately 4–12.5 days
at higher doses (White & Black, 2007).
See Exhibit 5-2 for estimated windows of
detection of some of the most commonly
prescribed benzodiazepines.
Exhibit 5-2. Benzodiazepines—Window of Detection*
Benzodiazepines Estimated Window of Detection
Short acting (e.g., triazolam) Up to 24 hours
Intermediate acting (e.g., alprazolam, clonazepam,
lorazepam, temazepam)
1–12.5 days
Long acting (diazepam) 5–8 days for diazepam
6–24 days for the active metabolite, nordiazepam
Chronic abuse of benzodiazepines Up to 30 days after the last dose
*Higher doses and some pathologies may extend the window of detection.
Source: White & Black (2007).
Cocaine
The Federal workplace cutoff concentration
for initial testing for cocaine is 150 ng/
mL, and conrmatory testing for cocaine
metabolite (benzoylecgonine) is 100 ng/mL
(SAMHSA, 2008).
Urine drug tests for cocaine detect cocaine’s
major metabolite, benzoylecgonine. The body
quickly metabolizes cocaine to its major
metabolite, benzoylecgonine, and neither
is stored in the body. Therefore, even with
chronic use, the window of detection is 1–3
days (Jufer, Walsh, Cone, & Sampson-Cone,
2006), with the clinical test cutoff of
300 ng/mL. The detection window may be
longer using the federally mandated cutoffs.
Urine immunoassay tests for cocaine are
highly specic and detect use of powder
(snorting or insufation), parenteral use, oral
ingestion, smoked, or use of crack cocaine.
Among the possibilities of products they
Clinical Drug Testing in Primary Care
5858
cannot distinguish is “Inca” tea or “coca”
tea—made from coca leaves—because they
contain cocaine. Ingestion of tea prepared
from coca leaves produces positive urine tests
for benzoylecgonine (Jenkins, Llosa, Montoya,
& Cone, 1996).
Immunoassay tests are highly specic for the
cocaine metabolite (benzoylecgonine) and do
not cross-react with other substances.
Marijuana/Cannabis
The SAMHSA workplace cutoff concentration
for cannabinoid metabolites is 50 ng/mL
for initial testing. The conrmatory testing
cutoff for cannabinoid metabolite (delta-9-
tetrahydrocannabinol-9-carboxylic acid) is 15
ng/mL.
Marijuana, the most commonly used illicit
drug, can be detected for prolonged periods
after regular use. The active principle of
marijuana, tetrahydrocannabinol (or THC)
has high lipid solubility. The THC that is
stored in fatty tissue gradually reenters the
bloodstream at very low levels, permitting
metabolism and eventual excretion. THC is
metabolized extensively in the liver.
The window of detection is highly dependent
on the quality of the marijuana, the
individual’s body fat content and metabolism,
chronicity of use, the individual’s state of
hydration when the urine sample is collected,
and the cutoff used by the laboratory (White
& Black, 2007). Approximate window of
detection times are as follows:
• Up to 3 days for single use
• Up to 4 days for moderate use
• Up to 10 days for heavy use
• 30–36 days for chronic, heavy use
Marijuana is easily detected by immunoassay.
Generally, laboratory tests for marijuana use
are designed to detect THC-COOH (11-nor-
Δ9-tetrahydrocannabinol-9-carboxylic acid;
commonly referenced as THC acid or THCA),
the major inactive metabolite of THC.
Laboratory tests are available with cutoff
concentrations of 20 ng/mL, 50 ng/mL, or
100 ng/mL, although the majority of
laboratories employ 50 ng/mL. The 20 ng/mL
cutoff is commonly used clinically (White &
Black, 2007). The 100 ng/mL cutoff is rarely
used due to its lack of sensitivity.
Conrmation by GC/MS tests should
be performed if the positive screening
test results have legal or other serious
implications for the patient. Some legal
food products are made from hemp seeds
(e.g., hemp seed oil, our, liquor, ale). These
products do not appear to be psychoactive,
but, after a person has ingested these food
products, THC metabolites have been
detected in urine specimens. However,
usually the THC concentrations in the food
products are too low to produce a positive
urine drug test result (Bosy & Cole, 2000).
Some proton-pump inhibitors have caused
positive tests on immunoassay (Gourlay et
al., 2010).
The literature is mixed on the test results
of passive exposure to marijuana. Under
extreme conditions (e.g., the person rides in
a closed car with people smoking marijuana),
passive exposure can lead to positive results
with a screening cutoff of 20 ng/mL. However,
the levels of marijuana metabolites found
in urine under less extreme passive
exposure conditions are below the 50 ng/mL
(employment-related) cutoff concentrations
and would not be detected (Cone et al., 1987;
Perez-Reyes, Di Guiseppi, & Davis, 1983).
Marinol and Sativex cause positive results
because they contain THC.
Opioids
Clinical urine opioid drug testing is done to
detect illicit opioid use, monitor adherence
to pain treatment with opioids (especially
in pain management clinics), and monitor
adherence to methadone treatment.
Practitioners need to be particularly careful
when interpreting urine drug test results
59
Chapter 5—Urine Drug Testing for Specic Substances
59
for opioids. It is essential to understand the
metabolism of this class of drugs to interpret
drug tests.
The term opioids includes both opiates and
opioids. Opioids are a group of compounds
that have pharmacological properties
similar to morphine and have afnity
toward the opiate receptors in the brain
(Dasgupta, 2008). The term opiates refers
to naturally occurring alkaloids (morphine
and codeine) obtained from the opium
poppy and semisynthetic alkaloids that are
partially derived from the opium poppy (i.e.,
buprenorphine, dihydrocodeine, heroin,
hydrocodone, hydromorphone, levorphanol,
oxycodone, and oxymorphone) (Dasgupta,
2008). Opioids include the synthetic
compounds that are structurally unrelated
to morphine (i.e., fentanyl, meperidine,
methadone, pentazocine, propoxyphene,
tramadol) (Dasgupta, 2008).
Opiate immunoassay tests were originally
designed to detect morphine and codeine as
target analytes to identify heroin use (Kwong,
2008a, 2008b). Morphine is a metabolite of
heroin (Warner, 2003). Many laboratories
use SAMHSA’s Federal workplace cutoff
concentrations for opiates and test for
morphine, codeine, and 6-acetylmorphone
(6-AM). However, for opiates, a cutoff
of 300 ng/mL is commonly preferred
clinically (White & Black, 2007). As heroin
is metabolized, 6-AM is produced, which
is then hydrolyzed to morphine. Thus, the
detection of 6-AM in the urine proves heroin
use, but 6-AM is eliminated quickly from
the body, making detection in urine possible
for only a few hours (Gourlay et al., 2010).
A typical opiate screen reports the presence
of only codeine and morphine. An expanded
opiate panel may also include hydrocodone
and hydromorphone and/or oxycodone and
oxymorphone (see Exhibit 5-3).
Exhibit 5-3. Opioids—Window of Detection*
Opioid Window of Detection Cutoffs
Buprenorphine Up to 4 days 0.5 ng/mL
Codeine 1–2 days 300 ng/mL
Heroin metabolite (6-acetylmorphine [6-AM]) 1–3 days 10 ng/mL
Hydrocodone 1–2 days 100 ng/mL
Hydromorphone 1–2 days 300 ng/mL
Methadone (maintenance dose) 3–11 days 300 ng/mL
Morphine 1–2 days 300 ng/mL
Oxycodone (immediate-release formulation) 1–1.5 days 100 ng/mL
Oxycodone (controlled-release formulation) 1.5–3 days 100 ng/mL
Oxymorphone (immediate-release formulation) 1.5–2.5 days 100 ng/mL
Oxymorphone (extended-release formulation) 1–4 days 100 ng/mL
*Higher doses and some pathologies may extend the window of detection.
Sources: Kronstrand et al. (2008); White & Black (2007).
Distinguishing between illicit opioid use
and the use of prescribed opioid medications
can be difcult. Immunoassay tests have
variable cross-reactivity with semisynthetic
opioids (i.e., hydrocodone, hydromorphone)
and may or may not detect their use.
The synthetic opioids (e.g., meperidine,
fentanyl, methadone) are structurally
dissimilar enough from morphine that they
are not detected in standard opioid urine
immunoassay tests, although some
cross-reactivity—especially with the
metabolites—may exist. Separate
immunoassay tests specically designed
for their detection must be used. Oxycodone
and its active metabolite, oxymorphone,
require a drug-specic test. Specic assays
for oxycodone are available as both POCTs
and laboratory tests. Specialized tests for
synthetic opioids must be ordered when
Clinical Drug Testing in Primary Care
6060
concerns exist about abuse or diversion
of synthetic opioid pain medications or to
monitor patients’ use of buprenorphine or
methadone. Many laboratories have specic
pain medication panels that test for codeine,
morphine, hydrocodone, hydromorphone,
oxycodone, fentanyl, and buprenorphine
(Gourlay et al., 2010). Buprenorphine has
potential for abuse, especially in the stand-
alone preparation—Subutex (Smith, Bailey,
Woody, & Kleber, 2007).
Poppy seeds can contain morphine and
codeine. Ingesting large amounts of poppy
seed or products containing poppy seeds
can cause a positive urine drug test result.
The urine drug test result will show that
morphine and, possibly, codeine are present,
and the practitioner needs to determine
whether poppy seeds are the source. The
original employment-related and clinical
cutoff concentration for morphine and codeine
was 300 ng/mL, but was increased to
2,000 ng/mL to avoid positive test from poppy
seed consumption (often cited as the “poppy
seed defense”). This higher cutoff minimized
opioid-positive test results from poppy seeds,
but also reduced the likelihood that opioid
use would be detected.
Methadone is a synthetic opioid used for
treatment of opioid dependence and chronic
pain and is not detected in standard opioid
drug tests. Specic tests for methadone and
its major metabolite EDDP (or 2-ethylidene-
1,5-dimethyl-3,3-diphenylpyrrolidine)
exist and are used to monitor adherence
to medication-assisted treatment and to
check for illicit drug use. These methadone
immunoassay tests have little cross-reactivity
with other opioids. Therefore, a positive
opioid drug test result for a patient on
methadone suggests the use of other opioids.
The cutoff concentration is generally set at
300 ng/mL and can detect methadone in urine
for several days after the last therapeutic dose.
To conrm that the patient has taken
methadone and is not simply adding it to a
urine specimen, the test for the methadone
metabolite, EDDP, can be ordered. If a
practitioner is caring for a patient on
methadone maintenance treatment for opioid
dependence, the practitioner can ask the
patient to sign a release of information to
obtain the patient’s urine test results from
the opioid treatment program.
Other Substances of Abuse
Testing information for other substances is
presented below.
PCP
The SAMHSA revised workplace cutoff
concentration for PCP is 25 ng/mL for initial
testing. The conrmatory testing cutoff for
PCP is 25 ng/mL. This cutoff is often used
for clinical purposes, as well. Federally
regulated laboratories are required to test
for PCP; other laboratories are not. Directors
of clinical laboratories may add PCP to their
screening drug panel if PCP use is prevalent
in the community. The window of detection
for PCP from casual use is 1.5–10 days
(urine pH-dependent) and for up to several
weeks with chronic use. The metabolite of
dextromethorphan can cross-react with PCP
and could cause a false positive.
When used to adulterate urine specimens,
table salt, sodium hypochlorite, sodium
hydroxide, detergent, and soap cause false-
negative test results (Jaffee et al., 2007).
However, these adulterants can be detected
if the pH and specic gravity of the urine
samples are checked.
Club Drugs
Club drugs generally include
gamma-hydroxybutyrate (GHB), ketamine,
unitrazepam (Rohypnol, or “Rooes”),
MDMA, MDA, and MDEA. Urine drug
screening tests do not generally screen for
club drugs. However, please see the section
above on amphetamines for information
about MDMA, MDA, and MDEA, and the
section on benzodiazepines for information on
unitrazepam (Rohypnol, or “Rooes”). New
drug tests may screen for some club drugs,
Chapter 5—Urine Drug Testing for Specic Substances
but routine drug tests cannot detect ketamine
or GHB. Testing for GHB can be done by using
GC or high-performance LC (LeBeau et al.,
2006). The window of detection for GHB is
generally less than 12 hours. Two commercial
enzyme-linked immunosorbent assays
(ELISAs) that test for ketamine are available
(Huang et al., 2007). For a single dose of
ketamine, detection is possible for about 3
days at a cutoff of 50 ng/mL (Baselt, 2004;
Cone & Huestis, 2007).
LSD
Very little of the parent drug, LSD, is
excreted in urine and it can be detected
for only approximately 4 hours. The
most abundant metabolite is nor-LSD
(N-desmethyl-LSD), which is generally
detected at a cutoff level of 0.5 ng/mL.
Conrmatory testing is usually done with
LC/MS or LC/MS/MS.
Inhalants
No standard drug test can detect inhalant
use. Most inhalants contain many compounds,
and no single assay can test for all of them.
Some laboratories can test for inhalants
using specially ordered tests, primarily with
GC. Collection of a specimen for inhalants
requires that the specimen be appropriately
and rapidly sealed to ensure that the volatile
inhalants are not lost.
Toluene is the main substance in many
inhalants. It is cleared from the body quickly,
leaving a short period to detect exposure.
Most laboratories are unable to test for this
substance. Urinary hippuric acid (UHA)
measurements can be adapted to detect
toluene inhalation, but they should be used
cautiously because a person’s metabolism can
raise the levels of UHA. Thiesen, Noto, and
Barros (2007) report that UHA levels higher
than 3.0 g/g creatinine indicate intentional
exposure.
6161
63
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Appendix B—Laboratory Initial
Drug-Testing Methods
Testing Method Description Advantages
Disadvantages/
Cautions
Cloned Enzyme Donor
Immunoassay (CEDIA)
• An immunoassay using enzyme
(ß-glucuronidase) fragments
engineered by recombinant DNA
techniques.
• Two fragments, the enzyme donor
and enzyme acceptor, are inactive
when separated.
• Based on competition for antibody
binding sites between drug
conjugated with enzyme donor (ED)
and drug in the specimen.
• Enzyme activity decreases when the
ED drug fragment is bound, so the
drug concentration in the specimen
can be measured by an increase of
enzyme activity.
• Same reliability
as EMIT in
screening for
barbiturate use.
• May produce
false-positive results
for amphetamines
and lysergic acid
diethylamide when
bupropion is used.
Enzyme-Multiplied
Immunoassay
Technique (EMIT)
• An immunoassay based on
competition for antibody binding
sites between drug in the specimen
and drug labeled with an enzyme.
• Enzyme activity decreases on
binding to the antibody, so the
drug when present in the specimen
can be measured by an increase in
terms of enzyme activity.
• Widely used.
• Simple to
conduct (same
as CEDIA or
KIMS).
• Poor performance
record (high rate
of false-positive
results in some
studies). Many
over-the-counter
(OTC) preparations
can cause false-
positive results for
amphetamines and
phencyclidine (PCP)
assays.
Enzyme-Linked
Immunosorbent Assay
(ELISA)
• A competitive binding enzyme
immunoassay using drug-specific
antibodies immobilized on the sides
of a microplate well.
• The most
versatile and
commonly used
immunoassay.
• Customized
tests developed
for different
settings,
substances,
purposes, and
matrices.
• Labor intensive.
• Poorly suited for
automation.
71
Clinical Drug Testing in Primary Care
Testing Method Description Advantages
Disadvantages/
Cautions
Fluorescence
Polarization
Immunoassay (FPIA)
• An immunoassay based on
competition between the drug in
the specimen and drug labeled with
a fluorophore.
• Light emitted by the fluorescently
labeled drug/antibody complex is
more polarized.
• The specimen’s fluorescence
polarization value is inversely related
to the drug concentration.
• Sensitive.
• Specific.
• Cannot be
automated
conveniently.
Kinetic Interaction of
Micro-particulates in
Solution (KIMS)
• An immunoassay based on the
principle of the kinetic interaction
of microparticles in a solution
where the drug content of the
urine is directly proportional to
the inhibition of the microparticle
aggregation.
• May be used
to test a wide
variety of drugs
of abuse.
• Cross-reacts
with some OTC
preparations
when testing for
amphetamines.
Sources: Armbruster, Hubster, Kaufman, & Ramon (1995); Center for Substance Abuse Treatment (2006b); Neerman (2006); Verebey,
Meenan, & Buchan (2005); Vidal & Skripuletz (2007).
72
• Separation is based on absorption, partition, ion exchange, and/or size
exclusion.
Appendix C—Laboratory Confirmatory
Drug-Testing Methods
Testing Method Description
Gas Chromatography (GC) • A technique for separating and analyzing compounds that can be
vaporized without chemicals.
High-Performance Liquid
Chromatography (LC)
• A chromatographic technique for separating and analyzing chemical
substances in solution.
GC/Mass Spectrometry
(GC/MS)
• A combined technique coupling an MS (mass spectrometer or mass
selective detector) with a GC instrument.
• After the GC has separated the analytes in a specimen, the components
enter the MS, which identifies and quantifies the separated analytes.
• The MS creates charged particles (ions) and separates them according to
their mass-to-charge ratio.
• The ions form unique mass spectra, which are used to identify analytes.
• Most common method of confirmation.
GC With Tandem
MS (GC/MS/MS)
• The same principles, as described above.
• The MS produces and isolates the ion of interest, which is then reacted
with a reagent gas to produce fragments.
• The MS scans the fragments (called the “productions”) to obtain
structural information.
• This method is more sensitive than GC/MS.
LC With MS (LC/MS) • LC can accommodate nonvolatile compounds.
• Separation is based on distribution of the solutes between a liquid mobile
phase and a stationary phase.
• MS phase is the same as described above.
• Widely used for pain management.
LC With Tandem MS
(LC/MS/MS)
• Described above, with two MS phases.
• Also used in pain management.
73
Appendix D—Laboratory Specimen
Validity-Testing Methods
Testing Method Analytes Description
Colorimetry Specific gravity,
pH, creatinine,
adulterants (general
or specific tests)
• A technique that compares the color developed in
a solution of a test material with that in a standard
solution, quantitated on the basis of the absorption of
light.
• The concentration of the analyte is determined by
visually noting the color or electronically measuring
the intensity of light at selected wavelengths (i.e.,
spectrophotometry).
Refractometry Urine-specific gravity • A method for determining the amount of solute (i.e.,
urinary total solids) in the urine by measuring the index of
refraction.
• A urine specific gravity refractometer displays specific
gravity values converted from refractive indices.
Potentiometry pH • An instrument (e.g., pH meter) that measures hydronium
ion activity and converts it into the negative logarithm
(base 10), which is the displayed pH.
Atomic Absorption
Spectrophotometry
Adulterants • A method in which the specimen atoms in the vapor
phase absorb ultraviolet or visible light and transition to
higher electronic energy levels.
• The analyte concentration is determined from the
amount of absorption of specific wavelengths.
Capillary
Electrophoresis (CE)
Adulterants • A technique based on the mobility of ions in an electric
field.
• Positively charged ions migrate toward a negative
electrode, and negatively charged ions migrate toward a
positive electrode.
• Ions have different migration rates depending on their
total charge, size, and shape and can therefore be
separated.
• CE is an electrophoretic method using a small-bore,
fused silica capillary tube.
Gas Chromatography/
Mass Spectrometry
(GC/MS)
Adulterants • Full-scan MS or selected ion monitoring identifies
unknown analytes.
• The identification of the analyte of interest relies on
a comparison with the mass spectra of an analyzed
reference standard or reference library spectra.
Inductively Coupled
Plasma/MS
Adulterants • A combined analytical method in which a vaporized
sample is introduced into a radio frequency-induced
plasma, is ionized, and then enters an MS for
identification and quantification.
75
Clinical Drug Testing in Primary Care
76
• A method that uses multiple wavelengths of light (or
other electronic transmissions) to identify an analyte.
Testing Method Analytes Description
Multi-Wavelength
Spectrometry
Adulterants
• The method generates corrected absorbance values that
are related to the analyte concentration.
Ion Chromatography Adulterants • A form of liquid chromatography that uses ion-exchange
resins to separate atomic or molecular ions based on
their interaction with the resin.
77
Appendix E—Glossary
adulterated specimen. A specimen containing either a substance that is not a normal
constituent for that type of specimen or containing an endogenous substance at a concentration
that is not a normal physiological concentration.
adulteration panel. Testing a specimen for substances that mask the presence of illegal drugs
in that specimen.
aliquot. A fractional part of a specimen.
analyte. Any material or substance subjected to analysis (testing).
chain of custody. Procedures to account for the integrity of each specimen or aliquot by tracking
its handling and storage from point of specimen collection to nal disposition of the specimen
and its aliquots.
concentration. Amount of a drug in a unit volume of biological uid expressed as
weight/volume. Urine concentrations are usually expressed as nanograms per milliliter (ng/
mL), micrograms per milliliter (ug/mL), or milligrams per liter (mg/L).
conrmatory drug test. A second analytical procedure performed on a different aliquot of the
original specimen to identify and quantify the presence of a specic drug or drug metabolite.
conrmatory validity test. A second test performed on a different aliquot of the original
specimen to support or deny the initial validity test result.
conjugate. A compound produced by the chemical joining of at least two other compounds.
creatinine. An endogenous substance appearing in the urine, commonly used to estimate
kidney functioning.
cutoff concentration or level. The measurement used to establish and report a specimen as
negative or positive.
deconjugate. The breaking down of a substance into the original compounds.
dilute specimen. A urine specimen whose creatinine is less than 20.0 mg/dL, but equal to or
greater than 2.0 mg/dL and whose specic gravity is less than 1.0030, but equal to or greater
than 1.0010.
diversion (of prescribed medications). The act of selling or giving away prescribed medications
instead of taking them as prescribed.
initial drug test. A test to differentiate a negative specimen from one that requires further
testing for drugs or drug metabolites. Also called a screening test.
Clinical Drug Testing in Primary Care
78
invalid result. The result reported when a scientically supportable analytical test result
cannot be established for a specimen.
matrix. The biological medium tested for the presence of drugs or drug metabolites.
Medical Review Ofcer (MRO). A licensed physician who reviews, veries, and reports a
specimen test result in regulated workplace programs.
metabolite. A compound produced by enzymatic or chemical means while in the body, usually to
a more water soluble form for easy excretion.
negative test result. The result reported by a laboratory when a specimen contains a drug or
drug metabolite less than a prespecied cutoff level or concentration.
pharmacogenomic. The genetic factors that inuence an organism’s response to or metabolism
of a drug or a medication.
point-of-care test (POCT). A drug or validity test conducted at the collection site to obtain an
initial or screening result on whether a specimen contains a drug or drug metabolite or is not a
valid specimen. Also called onsite, point-of-service, or point-of-collection test.
positive test result. The result reported by a laboratory when a specimen contains a drug or
drug metabolite greater than or equal to a prespecied cutoff level or concentration.
sample. A representative portion of a specimen or quality control material used for testing.
specimen. Fluid or tissue derived from the body collected for testing.
substituted specimen. A specimen that has been submitted in place of the patient’s urine, either
as evidenced by creatinine and specic gravity values that are outside the physiologically
producible ranges of human urine or is another person’s urine.
79
Appendix F—Expert Panel
Louis Baxter, M.D., Chair
Executive Medical Director
Professional Assistance Program of New
Jersey
Princeton, New Jersey
Lawrence S. Brown, Jr., M.D., M.P.H.
Senior Vice President
Addiction Research and Treatment
Brooklyn, New York
Paula Satterly Childs, Ph.D., D-ABFT
Director of Toxicology
Laboratory Corporation of America
Research Triangle Park, North Carolina
Edward Cone, Ph.D.
President
ConeChem Research LLC
Severna Park, Maryland
Dennis J. Crouch, M.B.A.
Associate Director for Sports Testing Services
Aegis Sciences Corporation
Nashville, Tennessee
Martin Doot, M.D. (Deceased)
Medical Director
Illinois Professionals Health Program
Des Plaines, Illinois
Mahmoud A. ElSohly, Ph.D., BCFE,
BCFM
President
ElSohly Laboratories, Inc.
Oxford, Mississippi
M. P. George, M.S.
Laboratory Operations Director
Quest Diagnostics, Inc.
Schaumburg, Illinois
Barbara L. Johnson, Esq.
Partner, Employment Department
Paul Hastings
Washington, D.C.
Donald Ian Macdonald, M.D., FASAM
Chief Medical Officer
Integrated Laboratory Services
Chestertown, Maryland
Susan McCall, M.D., M.P.H.
Medical Director
Oregon Health Professionals Program
Tigard, Oregon
Susan Neshin, M.D.
Medical Director
Jersey Shore Addiction Services
Asbury Park, New Jersey
Kent Peterson, M.D.
President
Occupational Health Strategies, Inc.
Charlottesville, Virginia
Gregory Rokosz, D.O., J.D.
Senior Vice President
Medical and Academic Affairs
St. Barnabas Medical Center
Livingston, New Jersey
Michel A. Sucher, M.D., FACEP, FASAM
Greenberg and Sucher, PC
Scottsdale, Arizona
Robert E. Willette, Ph.D.
President
Duo Research, Inc.
Eagle, Colorado
81
Appendix G—Consultants and Field
Reviewers
Consultants
Peter David Friedmann, M.D., M.P.H.
Assistant Professor
Brown Medical School
Departments of Medicine and Community
Health
Rhode Island Hospital
Providence, Rhode Island
Elizabeth A. Warner, M.D.
Medical Director
Ambulatory Services
Associate Professor
Department of Internal Medicine
University of South Florida
Tampa, Florida
Field Reviewers
Paul L. Cary, M.S.
Director
Toxicology and Drug Monitoring Laboratory
University of Missouri
Columbia, Missouri
Nancy L. Hamilton, M.P.A., CAP, CCJAP
Chief Executive Officer
Operation PAR
Pinellas Park, Florida
Carolyn Hardin, M.P.A.
Director
National Drug Court Institute
Alexandria, Virginia
Jim Heit, M.T.
Sterling Reference Laboratories
Tacoma, Washington
Ron Jackson, M.S.W.
Director
Evergreen Treatment Services
Seattle, Washington
Jason Kletter, Ph.D.
President
Bay Area Addiction Research and Treatment
(BAART)
San Francisco, California
83
Appendix H—Acknowledgments
Numerous people contributed to the development of this Technical Assistance Publication
(TAP), including TAP expert panel members, consultants, and eld reviewers (see Appendix F
and Appendix G, respectively).
This publication was produced under the Knowledge Application Program (KAP), a Joint
Venture of The CDM Group, Inc., and JBS International, Inc. (JBS), for the Substance Abuse
and Mental Health Services Administration.
Lynne MacArthur, M.A., A.M.L.S., served as the JBS KAP Executive Project Co-Director, and
Barbara Fink, RN, M.P.H., served as the JBS KAP Managing Project Co-Director. Other JBS
KAP personnel included Wendy Caron, Editorial Quality Assurance Manager; and Frances
Nebesky, M.A., Copy Editor.
Technical Assistance Publications (TAPs) include:
TAPs 1–9, 25* These TAPs have been archived and are no longer available.
TAP 10 Rural Issues in Alcohol and Other Drug Abuse Treatment
TAP 11 Treatment for Alcohol and Other Drug Abuse: Opportunities for Coordination*
TAP 12 Approval and Monitoring of Narcotic Treatment Programs: A Guide on the Roles of Federal and State
Agencies*
TAP 13 Confidentiality of Patient Records for Alcohol and Other Drug Treatment BKD156
TAP 14 Siting Drug and Alcohol Treatment Programs: Legal Challenges to the NIMBY Syndrome BKD175
TAP 15 Forecasting the Cost of Chemical Dependency Treatment Under Managed Care: The Washington State
Study*
TAP 16 Purchasing Managed Care Services for Alcohol and Other Drug Abuse Treatment: Essential Elements
and Policy Issues*
TAP 17 Treating Alcohol and Other Drug Abusers in Rural and Frontier Areas BKD174
TAP 18 Checklist for Monitoring Alcohol and Other Drug Confidentiality Compliance*
TAP 19 Counselor’s Manual for Relapse Prevention With Chemically Dependent Criminal Offenders (SMA)
06-4217
TAP 20 Bringing Excellence to Substance Abuse Services in Rural and Frontier America BKD220
TAP 21 Addiction Counseling Competencies: The Knowledge, Skills, and Attitudes of Professional Practice
(SMA) 12-4171
TAP 21-A Competencies for Substance Abuse Treatment Clinical Supervisors (SMA) 12-4243
TAP 22 Contracting for Managed Substance Abuse and Mental Health Services: A Guide for Public
Purchasers BKD252
TAP 23 Substance Abuse Treatment for Women Offenders: Guide to Promising Practices (SMA) 08-3929
TAP 24 Welfare Reform and Substance Abuse Treatment Confidentiality: General Guidance for Reconciling
Need to Know and Privacy BKD336
TAP 26 Identifying Substance Abuse Among TANF-Eligible Families (SMA) 05-4089
TAP 27 Navigating the Pathways: Lessons and Promising Practices in Linking Alcohol and Drug Services
With Child Welfare*
TAP 28 The National Rural Alcohol and Drug Abuse Network Awards for Excellence 2004, Submitted and
Award-Winning Papers (SMA) 12-4183
TAP 29 Integrating State Administrative Records To Manage Substance Abuse Treatment System Performance
(SMA) 12-4268
TAP 30 Buprenorphine: A Guide for Nurses (SMA) 09-4376
TAP 31 Implementing Change in Substance Abuse Treatment Programs (SMA) 09-4377
TAP 32 Clinical Drug Testing in Primary Care (SMA) 12-4668
*Archived but available in electronic format at http://kap.samhsa.gov.
TAPs may be ordered from SAMHSA’s Publications Ordering Web page at http://store.samhsa.gov.
Or, please call SAMHSA at 1-877-SAMHSA-7 (1-877-726-4727) (English and Español).
HHS Publication No. (SMA) 12-4668
Substance Abuse and Mental Health Services
Administration
Printed 2012