Gas Chromatography- Mass Spectrometry

National Historic Chemical Landmarks

Chemists and Chemistry that Transformed Our Lives

Gas Chromatography-

Mass Spectrometry

The Dow Chemical Company

American Chemical Society

“GC-MS is

indispensable

in the ﬁelds of

environmental

science, forensics,

health care,

medical and

biological

research, health

and safety,

the ﬂavor and

fragrances

industry, food

safety, packaging,

and many others.”

— Gas

Chromatography

and Mass

Spectrometry: A

Praccal Guide

“GC-MS is the synergistic combination of two powerful microanalytical techniques. The gas

chromatograph separates the components of a mixture in time, and the mass spectrometer

provides information that aids in the structural identification of each component.”

— Gas Chromatography and Mass Spectrometry: A Practical Guide

In Star Trek, Mr. Spock’s hand-held

tricorder can instantly tell what

something is made of. We don’t

have tricorders yet, but we’re getting

close. Portable devices just a little

too big to hold in one hand are used

today to analyze samples at crime

scenes, fires, and other places where

time is of the essence.

The technology had its start 60

years ago in Midland, Michigan,

with the pairing of two powerful

analytical techniques — gas

chromatography (GC) and mass

spectrometry (MS). By coupling

the ability of GC to separate a

chemical mixture with the ability

of MS to identify its components,

the new, combined technique

proved revolutionary. GC-MS is

now routinely used for speedy

analysis in forensics, environmental

monitoring, drug testing of athletes,

and other applications.

EARLY MASS SPEC

The origin of MS dates to the early

20th century, when Sir Joseph John

“J. J.” Thomson of the University

of Cambridge was studying the

structure and behavior of atoms

and molecules. Building on his and

others’ previous research, Thomson

in 1907 developed a device that

created an electric arc in a container

holding a small amount of a gas.

The electrical discharge stripped

electrons from the gas molecules,

creating a variety of positively

charged ions with a range of masses.

In the presence of an electric field,

the ions could be accelerated

and manipulated. When pushed

through a magnetic field, the stream

of ions bent and separated like

light through a prism, Thomson

discovered. The ions then struck a

fluorescent screen or photographic

plate at locations dictated by their

mass-to-charge ratios, creating

bright streaks where they landed.

The resulting patterns were

different for different materials,

so Thomson could identify pure

materials by their unique patterns.

Given this background, some

historians credit Thomson as the

inventor of MS. Most others look to

his assistant, Francis W. Aston, who

made multiple improvements and

won a Nobel Prize in Chemistry in

1922 for the development of the first

workable mass spectrograph.

By the mid-20th century, more-

advanced mass spectrometers

became commercially available.

For each sample analyzed, the ions

yielded a chart or “mass spectrum”

from which the original molecule’s

structure could be inferred.

If analyzed under identical

conditions, any given compound

always produces the same family

of ions, creating a unique mass

spectrum for each compound.

When two or more compounds

are present, the mass spectrum is

a combination of the spectrum of

each component. The result may be

so messy it can’t be used to identify

the components, meaning MS works

well for pure materials, but not so

well for mixtures.

GC’S ORIGINS

The first widely noticed introduction

of GC was made in 1951-52 by

Anthony T. James and Archer J. P.

Martin of the National Institute

for Medical Research, in London.

Commercial instruments soon

followed. The technique built on

earlier chromatography research by

multiple scientists, including work

that earned Martin and Richard L.

M. Synge the 1952 Nobel Prize in

Chemistry.

GC relies on the differing affinities

of vapor components for surfaces.

In a gas chromatograph, a mixture

is first vaporized and picked up by

an inert gas. This carrier gas is then

pushed into a tube or “column”

that in early days was packed with

small, solid particles. Due to their

different chemical properties some

compounds interact with the

solid surfaces more strongly than

others and are slowed in their race

through the column. At the end of

the column is a specialized detector

that produces a signal as each

compound exits the column, with

the signal intensity corresponding

roughly to the relative amount of

each component. Plotting the signal

on graph paper (or in later years,

on a computer screen) gives a peak

for each component in the mix. The

pattern of peaks or “chromatogram,”

is reproducible for any given sample,

assuming it’s run through the

column in the same way.

Many GC columns separate

compounds approximately

by boiling point. Low-boiling

substances move faster and

have lower retention times

than higher-boiling substances.

However, boiling points aren’t

unique, so different chemicals

can have the same retention time.

That means chromatographic

retention time alone isn’t enough

to unambiguously identify a

component in a mixture.

GC & MS PAIR UP

In 1950, Fred McLafferty and Roland

Gohlke, two Dow Co. researchers,

dramatically enhanced the analytical

power of GC by coupling it with MS.

Adding MS allowed each component

exiting the gas chromatograph to be

analyzed separately.

Taken together, the mass spectra

and the chromatographic peaks

allowed unambiguous identification

of each component. For an unknown

mixture, the mass spectrum for

each peak can narrow the possible

identity of each component. Known

standards can then confirm the

identifications if both retention time

and mass spectra match.

In coupling GC with MS, Gohlke

and McLafferty overcame many

issues. Chromatography columns

weren’t commercially available, so

they had to make their own. GC

operates under pressure, whereas

MS operates in vacuum. They had

to devise a valving arrangement

that would leak only a little of the

total material coming from the gas

chromatograph, without altering

retention times. They also had to

rapidly capture the fleeting mass

spectrum for each compound:

Lab computers didn’t exist at the

time, so they photographed each

spectrum as it briefly appeared on

an oscilloscope.

After making a gas chromatograph

and valve they thought would

work, the researchers met with

William C. Wiley and Daniel B.

Harrington at Bendix Aviation Corp

in Southfield, Michigan. There,

McLafferty and Gohlke coupled

their gas chromatograph with a

very fast mass spectrometer that

Wiley and his Bendix colleagues

had developed. In short order

they produced spectra of acetone,

benzene, carbon tetrachloride, and

toluene from a mixture of these

compounds.

After this first successful

demonstration of a paired GC-MS

instrument in the winter of 1955-56,

McLafferty and Gohlke convinced

Dow to buy a Bendix mass

spectrometer. Gohlke continued

the GC-MS experiments at Dow’s

spectroscopy lab with numerous

colleagues. He and McLafferty

first presented their results at the

American Chemical Society’s April

1956 national meeting. Gohlke

published the first journal article

about their GC-MS work in Analytical

Chemistry in 1959.

Around this same time, Joseph C.

Holmes and Francis A. Morrell of

Philip Morris Inc. also coupled GC

and MS using a slower spectrometer

made by Consolidated Engineering

Corp., an approach the Dow

scientists had rejected. Holmes and

Morrell initially announced their

findings at an American Society

for Testing and Materials MS

committee meeting in Cincinnati

in May 1956. They wrote up their

findings in a 1957 paper in Applied

Spectroscopy.

Holmes and Morrell are credited by

some for the development of GC-MS

due to the independent but near-

simultaneous demonstration. None

of these four scientists patented

the technology, leaving other

researchers and companies free to

adapt and improve on the method.

FURTHER DEVELOPMENT

Mass spectrometers work on several

different principles. The Bendix

spectrometer used by Gohlke

and McLafferty was a “time-of-

flight” instrument that produced a

spectrum based on the time it took

ions to traverse a long tube. Bendix

began marketing a GC-MS device

in 1959, but the first commercial

success was LKB Instruments Inc.’s

Model 9000, which debuted in

1965. The LKB instrument used a

magnet to disperse the ions just like

Thomson did years earlier. Other

companies followed suit, including

Finnigan Instruments, Perkin Elmer,

and Hewlett Packard, now Agilent.

Several other advances paved the

way for GC-MS to go mainstream.

The instruments became

smaller and less expensive. With

developments in computing power,

libraries of mass spectra could be

compiled and computers could

identify chromatographic peaks.

GC-MS is an essential technology in

modern analytical chemistry labs.

Applications include development of

new pharmaceuticals and analysis

of their purity, detection of chemical

warfare agents and explosives,

screening of athletes’ urine for

banned performance-enhancing

substances, and analyzing soil

samples on Mars. Portable units can

now be carried in one arm for on-

site analysis, bringing us closer than

ever to Star Trek’s vision.

20 MIN Start

time

Mass Spectrum

Chromatogram

packed

column

sample

70V

split

valve

vent

detector

oscilloscope

mass spectrum

camera

time-of-flight MS

chromatogram

Time

3D Method

time

total ion

signal

mass

spectrum

Signal Intensity

Mass Spectrum

Time

A NATIONAL HISTORIC CHEMICAL LANDMARK

In this sample from 1959, the mass spectrometer produc-

es characteristic spectra for each component separated

by the gas chromatograph. Credit: Mark Jones

This schematic

shows the major

components of

an early gas

chromatograph-

mass spectrometer.

Not to scale.

Credit: Mark Jones

20 MIN Start

time

Mass Spectrum

Chromatogram

packed

column

sample

70V

split

valve

vent

detector

oscilloscope

mass spectrum

camera

time-of-flight MS

chromatogram

Time

3D Method

time

total ion

signal

mass

spectrum

Signal Intensity

Mass Spectrum

Time

Acknowledgments:

Written by Mark Jones.

The author wishes to thank contributors to and reviewers of this booklet, all

of whom helped improve its content, especially members of the ACS NHCL

Subcommittee.

The nomination for this Landmark designation was prepared by the Midland

Section of the ACS and The Dow Chemical Co.

Cover: Fred McLafferty and Roland Gohlke (in foreground) work on a Bendix

mass spectrometer at Dow circa 1960. Courtesy of Dow.

Printed by CAS, a division of the American Chemical Society

American Chemical Society

Bonnie Charpentier, President

Luis Echegoyen, President-Elect

Peter Dorhout, Immediate Past President

John Adams, Chair, Board of Directors

Midland Section of the ACS

Amanda Palumbo, Section Chair

Jaime Curtis-Fisk, Section Chair at time

of landmark nomination

ACS National Historic Chemical

Landmarks Subcommittee

Vera Mainz, NHCL Subcommittee

Chair, University of Illinois at Urbana-

Champaign, retired

Mary Ellen Bowden, Science History

Institute, retired

Carmen Giunta, Le Moyne College

David Gottfried, Georgia Institute of

Technology

Arthur Greenberg, University of New

Hampshire

William Jensen, University of Cincinnati

Mark Jones, The Dow Chemical Co.

Diane Krone, Northern Highlands

Regional High School, retired

Seymour Mauskopf, Duke University,

emeritus

Andreas Mayr, Stony Brook University

Daniel Menelly, The DoSeum

Michal Meyer, Science History Institute

William Oliver, Northern Kentucky

University, emeritus

Alan Rocke, Case Western Reserve

University, emeritus

Heinz Roth, Rutgers University

Jeffrey Sturchio, Rabin Martin

Richard Wallace, Georgia Southern

University

Sophie Rovner, ACS Staff Liaison and

NHCL Program Manager

American Chemical Society

National Historic Chemical Landmarks Program

External Affairs & Communications

Office of the Secretary and General Counsel

1155 Sixteenth Street, NW

Washington, D.C. 20036

landmarks@acs.org

www.acs.org/landmarks

Gas Chromatography-Mass Spectrometry

A National Historic Chemical Landmark

The American Chemical Society (ACS) honored The Dow Chemical Company’s

innovation in combining gas chromatography and mass spectrometry with a

National Historic Chemical Landmark (NHCL) in a ceremony at the H Hotel in

Midland, Michigan, on June 8, 2019. The commemorative plaque reads:

In 1955-56, Dow Chemical scientists Fred McLafferty and Roland Gohlke first

demonstrated the combination of gas chromatography (GC) and mass spec-

trometry (MS) to identify individual substances in a mixture. This was the first

coupling of a separation technology with a spectrometry technique to provide

rapid characterization of chemical components. GC-MS remains one of the

most powerful, flexible, and widely used tools for analyzing chemical mixtures

in drug screening, forensic, environmental, and trace analysis, as well as other

applications.

About the National Historic Chemical Landmarks Program

ACS established the NHCL program in 1992 to enhance public appreciation

for the contributions of the chemical sciences to modern life in the U.S. and

to encourage a sense of pride in their practitioners. The program recognizes

seminal achievements in the chemical sciences, records their histories and

provides information and resources about NHCL achievements. Prospective

subjects are nominated by ACS local sections, divisions, or committees,

reviewed by the ACS NHCL Subcommittee, and approved by the ACS Board

Committee on Public Affairs and Public Relations.

ACS, the world’s largest scientific society, is a not-for-profit organization

chartered by the U.S. Congress. ACS is a global leader in providing access to

chemistry-related information and research through its multiple databases,

peer-reviewed journals, and scientific conferences. Its main offices are in

Washington, D.C., and Columbus, Ohio.