á233ñ ELEMENTAL IMPURITIES—PROCEDURES
Change to read:
INTRODUCTION
This chapter describes two analytical procedures (Procedures 1 and 2) for the evaluation of the levels of the elemental impuri-
ties. The chapter also describes criteria for acceptable alternative procedures.
2S (USP38)
By means of validation
2S (USP38)
stud-
ies, analysts will confirm that the analytical procedures described herein
2S (USP38)
are suitable for use on specified material.
Use of Alternative Procedures
The chapter also describes criteria for acceptable alternative procedures. Alternative procedures that meet the validation re-
quirements herein may be used in accordance with General Notices and Requirements 6.30, Alternative and Harmonized Methods
and Procedures. Information on the Requirements for Alternate Procedure Validation is provided later in this chapter.
2S (USP38)
Speciation
The determination of the oxidation state, organic complex, or combination is termed speciation. Analytical procedures for
speciation are not included in this chapter, but examples may be found elsewhere in USP–NF and in the literature.
Change to read:
COMPENDIAL PROCEDURES 1 AND 2
System standardization and suitability evaluation using applicable reference materials should be performed on the day of
analysis.
2S (USP38)
Procedure and Detection Technique
Procedure 1 can be used for elemental impurities generally amenable to detection by inductively coupled plasma–atomic
(optical) emission spectroscopy (ICP–AES or ICP–OES). Procedure 2 can be used for elemental impurities generally amenable to
detection by ICP–MS. Before initial use, the analyst should verify that the procedure is appropriate for the instrument and sam-
ple used (procedural verification) by meeting the alternative procedure validation requirements below.
Sample Preparation
Forms of sample preparation include Neat, Direct aqueous solution, Direct organic solution, and Indirect solution. The selection
of the appropriate sample preparation depends on the material under test and is the responsibility of the analyst. When a sam-
ple preparation is not indicated in the monograph, an analyst may use any of the following appropriately
validated
2S (USP38)
preparation procedures. In cases where spiking of a material under test is necessary to provide an acceptable signal intensity,
the blank should be spiked with the same Target elements, and where possible, using the same spiking solution. Standard solu-
tions may contain multiple Target elements. [NOTE—All liquid samples should be weighed.]
Neat: Used for liquids or alternative procedures that allow the examination of unsolvated samples.
Direct aqueous solution: Used when the sample is soluble in an aqueous solvent.
Direct organic solution: Used where the sample is soluble in an organic solvent.
Indirect solution: Used when a material is not directly soluble in aqueous or organic solvents. Total metal extraction is the
preferred sample preparation approach to obtain an indirect solution.
2S (USP38)
Digest the sample using the
2S (USP38)
Closed ves-
sel digestion procedure provided below or one
2S (USP38)
similar to it.
2S (USP38)
The sample preparation scheme should yield
sufficient sample to allow quantification of each element at the limit specified in the corresponding monograph or chapter.
Closed vessel digestion: This sample preparation procedure is designed for samples that must be digested in a Concentrated
acid using a closed vessel digestion apparatus. Closed vessel digestion minimizes the loss of volatile impurities. The choice of a
Concentrated acid depends on the sample matrix. The use of any of the Concentrated acids may be appropriate, but each intro-
duces inherent safety risks. Therefore, appropriate safety precautions should be used at all times. [NOTE—Weights and volumes
provided may be adjusted to meet the requirements of the digestion apparatus used.]
An example procedure that has been shown to have broad applicability is the following. Dehydrate and predigest 0.5 g of
primary sample in 5 mL of freshly prepared Concentrated acid. Allow to sit loosely covered for 30 min in a fume hood. Add an
additional 10 mL of Concentrated acid, and digest, using a closed vessel technique, until digestion or extraction is complete.
Second Supplement to USP 38–NF 33
Chemical Tests / á233ñ Elemental Impurities—Procedures 1