Gas Chromatography–Mass Spectrometry
E Stauffer, Commissariat d’identification judiciaire, Police cantonale Fribourg, Fribourg, Switzerland
ã 2013 Elsevier Ltd. All rights reserved.
Glossary
Chromatogram A graphical representation of
chromatographic data. It is the record of detector response as
a function of time.
Extracted ion chromatogram Graphical representation of
the abundance of a single ion versus retention time (RT).
Abbreviated EIC.
Extracted ion profile Graphical representation of the
abundance of the sum of several ions versus RT. Abbreviated
EIP.
Gas chromatography A separation technique in which the
mobile phase is a gas. Gas chromatography is always carried
out in a column. Abbreviated GC.
Gas chromatography–mass spectrometry A separation
technique (gas chromatography) coupled with a detection
technique (mass spectrometry). Abbreviated GC–MS.
m/z ratio Mass-to-charge ratio: The mass of an ion divided
by its charge.
Mass spectrometry An analytical technique that is used to
identify unknown compounds, to quantify known
Abbreviations
EIC Extracted ion chromatogram
EIP Extraction ion profile
FID Flame ionization detector
GC Gas chromatography or gas chromatograph
GCGC Two-dimensional comprehensive gas
chromatography
Introduction
Chromatographic techniques have the power to separate
analytes from complex mixtures. However, separating these
analytes would not be useful if it was not possible to either
detect them or, better yet, to identify them. For this reason,
different detectors have been used throughout the years. With
simple thin-layer chromatography, or paper chromatography,
the naked eye, or an alternate light source, would suffice to
detect some analytes. Eventually, a chemical reaction would be
triggered. On the more modern gas chromatograph, flame
ionization (FID) or photoionization detectors are used,
depending on the type of analytes to be detected.
However, the common ground of all these detectors is that
they only provide two types of information: the number of
analytes and their concentration. Nowadays, particularly in the
forensic field, this information does not suffice. One needs to
know the identity of a compound or of a series of compounds
from a complex mixture.
596 Encyclopedia of Forensic Sciences, Second Edition
compounds, and to elucidate the structure and chemical
properties of molecules. This is done by converting
components of a sample into rapidly moving gaseous ions
and separating them on the basis of their mass/charge ratio.
Abbreviated MS.
Resolution In chromatography, the measure of the
separation of two components. It is a function of the peak
width and RT. In mass spectrometry, the measure of the
ability of the instrument to distinguish ions of different
masses.
Retention time The length of time required for a compound
to pass through a chromatographic column and be detected.
Total ion chromatogram Graphical representation of the
abundance of a full scan range versus RT. Abbreviated TIC.
Two-dimensional comprehensive gas
chromatography A procedure in which all of the separated
sample components are subjected to an additional
separation step. This is achieved by coupling (using a
thermal modulator) two different chromatographic
columns. Abbreviated GCGC.
MS Mass spectrometry or mass spectrometer
m/z Mass-to-charge ratio
SIM Selected ion monitoring
TIC Total ion chromatogram
TOF Time-of-flight
Mass spectrometry does not simply detect the presence or
absence of analytes; it provides structural information about
the molecule, often leading to its identification. As such, it is
an extremely powerful instrument, but one which quickly
becomes impractical when analyzing complex mixtures of ana-
lytes. As a matter of fact, its optimal use consists in analyzing
pure compounds. This is when the chances of identifying the
unknown compounds are greatest.
Thus, the separation power of gas chromatography and the
analytical power of mass spectrometry needed to be combined
in one full analytical instrument in order to exploit the capa-
bilities of both techniques to their maximum. Chromatogra-
phy was invented in 1906 by Russian chemist Mikhail
Semenovich Tswett and mass spectrometry in 1913 by British
physicist Joseph John Thomson. Gas chromatography was
invented in 1952 by James and Martin, which allowed the
first combined use of gas chromatography and mass spectrom-
etry as a hyphenated technique in 1956 by Roland Gohlke and
Fred McLafferty.
http://dx.doi.org/10.1016/B978-0-12-382165-2.00249-X

The typical setup of a gas chromatograph–mass spectrome-
ter is shown in Figure 1. The sample is injected in the gas
chromatograph, separated through the column, then goes
through the transfer line and is analyzed in the mass spectrom-
eter. A computer controls the overall instrument.
Gas chromatography–mass spectrometry (GC–MS) does
not simply add the capability of one to another; it literally
multiplies both capabilities and leads to a full analytical in-
strument. While the specificities of gas chromatography alone
(with a simple detector such as FID) and mass spectrometry
alone are not great, the combination of both results in an
enormous increase in specificity. If two compounds were not
to be separated by the chromatographic process, there is a good
chance that they would exhibit different structural data and,
thus, be distinguished through the mass spectrometer. Simi-
larly, two compounds exhibiting a very close mass spectrum
may have a good chance of being separated by the chromato-
graphic process, thus allowing for their distinction. However,
one will always find compounds that have very close chro-
matographic and structural characteristics, for which GC–MS
will not be able to make a distinction. This is the case with
some structural isomers.
Multiplied Powers
When considering a regular chromatogram, obtained with a
simple detector such as FID, the sole information available is
the curve constituting the chromatogram. One can extract the
retention time (RT) and the peak area, thus the concentration
of the analyte if a calibration curve is available. However, it is
very possible that another analyte elutes exactly at the same
time as the analyte of interest. As such, it is not possible to be
sure that the peak in question is the sought-after analyte.
When considering a chromatogram obtained from a
GC–MS, the resulting data actually hides another whole layer
Injection port
Inlet
Column
Mass Oven
Computer spectrometer Gas chromatograph
controller and
data acquisition
Transfer line
Figure 1 Typical setup of a gas chromatograph–mass spectrometer. Reproduced from Stauffer E, Dolan JA, and Newman R (2008) Fire Debris
Analysis, p. 246. Burlington, MA: Elsevier Academic Press. Copyright ã 2008, Elsevier.
Methods | Gas Chromatography–Mass Spectrometry 597
of information. For each point on the curve, it is possible to
extract a mass spectrum, providing the structural information
of the analyte(s) eluting at that time. Figure 2 illustrates this.
This information consists of a series of mass-to-charge ratio
(m/z) peaks with their relative abundance. The most important
of these peaks is the molecular ion peak, which corresponds
to the unfragmented compound, and the base peak, the most
intense peak of the spectrum, normalized to 100%. The other
peaks represent the fragments of the molecule, fragments with
distribution and relative abundances that are characteristic of
the structure of the molecule.
As such, in addition to RT data, one benefits from structural
data to identify an analyte. If each analyte in the complex
mixture is completely separated from the others, it is then pos-
sible to identify with certainty the nature of each analyte. This is
where the power of GC–MS comes into play: the capability of
identifying almost every component from a complex mixture.
Different Ways of Looking at Data
One great advantage of GC–MS lies in the different ways it is
possible to acquire and look at data. Typically, one acquires
data using a full scan range, which means that the mass spec-
trometer is configured to acquire all the m/z within a given
range (e.g., 33–400 m/z). The resulting data is called a total ion
chromatogram (TIC). It can be seen as a chromatogram iden-
tical to one that would be obtained with another simple detec-
tor, except that each data entry making the chromatographic
pattern contains a full mass spectrum.
The great advantage of the TIC is that all the analytes
present in a given sample are detected and recorded. Thus,
the chromatogram truly and fully represents the overall con-
tent and the analyst has a good panoramic view of what is in
the sample. A few disadvantages also exist. The first one is that
carrying out a full scan takes time and the resolution of
Pressure regulator
Flow Gas filters Carrier
controller
gas
supply
598 Methods | Gas Chromatography–Mass Spectrometry

105
100
1,2,4-trimethylbenzene
Abundance

Relative abundance
80

60
120
40

20 77 91
51 65
0
0 50 100 150
3 000 000 Mass-to-charge ratio (m/z)

43
100
Decane
57

Relative abundance
80

60

40 29
71
85
2 000 000 20
99 142
0
0 50 100 150
Mass-to-charge ratio (m/z)

128
100 Naphthalene

Relative abundance
80

1 000 000 60

40

20
51
0
0 50 100 150
Mass-to-charge ratio (m/z)

0
2 3 4 5 6 7 8 9 10 11 12 13 14 15 Time
Carbon # 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Figure 2 Total ion chromatogram of a 75% evaporated gasoline sample. Each point on the chromatogram contains a full mass spectrum,
as shown with the peaks of 1,2,4-trimethylbenzene, decane and naphthalene.

the chromatogram may not be optimal, thus not allowing for a
full separation of some analytes. Second, if one is only inter-
ested in the presence of a given or a set of given analytes, these
may not stand out within the overall pattern of the mixture.
Third, the sensitivity of the full scan range is not as good as
the one that would result from the scan of just a few ions. The
more m/z are scanned, the worse the sensitivity. Thus, some
trace analytes may simply not be detected or distinguished
from the background signal.
As an alternative, it is possible to use a selected ion moni-
toring (SIM) rather than a full scan. In this situation, the user
decides which ions must be monitored. The MS will then scan
only for these m/z and ignore all of the others. This allows for a
quasi-complete suppression of the matrix interferences: only
the analytes sought after are detected. It also significantly im-
proves the sensitivity since each scan covers only a couple of
dozens m/z rather than a full range of 300 or more m/z, for
example. One major disadvantage in this configuration is
that the analyst completely loses the overall view of the sample.
Because only a partial image of what is in the sample is
obtained, it is not possible to take into account the overall
composition of the sample during the interpretation of the
results. If the full scan corresponds to a wide-angle view, SIM
would correspond to a super telephoto view.
Some analyses are better carried out using SIM and some
others using a full scan. Analyzing a sample of unknowns
would naturally require a full scan, since one does not know
in advance which analytes are sought after. Conversely, per-
forming routine analysis for some specific known metabo-
lites in trace amounts, for which their presence and quantity
are not influenced by the content of the matrix, is best
performed using a SIM configuration. In fire debris analysis,
for example, even though the analytes sought after are quite
known, it is not recommended to carry out only SIM. As a
matter of fact, it is important to have a good view of the
content given off by the sample’s matrix, since it is taken
into consideration in the interpretation of the results. How-
ever, it is recommended in some instances, after performing
a full scan range, to carry out a second analysis, under a SIM
mode, to improve the sensitivity of the GC–MS and to
provide further data.
When using a full scan, it is still possible to benefit from the
mass spectral data. Starting from the TIC, one can selectively
display some individual m/z, leading to an extracted ion chro-
matogram (EIC), as shown in Figure 3, or a sum of several m/z,
leading to an extracted ion profile (EIP), as shown in Figure 4.
When comparing Figures 3 and 4 to Figure 2, one quickly
realizes the advantage of extracted ions in interpreting chro-
matograms and identifying classes of compounds.
This provides the advantage of first having a complete view
of the sample through the full scan and second, looking at
specific compound-related patterns through the EIC or EIP.
This allows the data to be filtered through the partial removal
of matrix interferences or other analytes and for the pertinent
data to be revealed. The great advantage of EIC and EIP is that it
does not filter at the data acquisition, thus the full data always
remains available.
Requirements
In order to combine a gas chromatograph to a mass spectrom-
eter, a few conditions must be met.
First of all, the sample must be suitable for injection into
the mass spectrometer. This is naturally achieved because the
mobile gas phase exiting the GC with the analytes is perfectly
suitable for entry into the MS, where it will first be ionized and
then filtered, to be finally detected.
 Methods | Gas Chromatography–Mass Spectrometry 599

Abundance

50 000
Alkane profile
(ions 57 + 71 + 85 + 99)

25 000

Cycloalkane profile
20 000
(ions 55 + 69 + 83)

10 000

0
2 3 4 5 6 7 8 9 10 11 12 13 14 15 Time
Carbon # 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
Aromatic profile
(ions 91 + 105 + 119)
1 000 000

500 000

Indanes profile
300 000 (ions 117 + 118 + 131 + 132)

200 000

100 000

Polynuclear aromatic profile

500 000
(ions 128 + 142 + 156)

250 000

0
5 6 7 8 9 10 Time
Carbon # 9 10 11 12 13 14 15

Figure 3 Example of extracted ion profiles from a 75% evaporated gasoline sample. One can clearly see the patterns exhibited by the different
classes of compounds. Reproduced from Stauffer E, Dolan JA, and Newman R (2008) Fire Debris Analysis, p. 316. Burlington, MA: Elsevier
Academic Press. Copyright ã 2008, Elsevier.

Second, it is important to realize that in order to obtain a
mass spectrum, a certain amount of time is required. This time
depends on the type of detector and the scan range (typically
something like 30–400 m/z). The larger the scan range, the
longer the scan takes. In order to obtain full separation of
coeluting compounds, the resolution of the chromatogram
must be high enough to allow for the separation of the peaks.
Thus, if two compounds elute within 4 s and the MS makes one
full scan every 4 s, the compounds will not be separated and
the specificity of the instrument will strongly suffer.
600 Methods | Gas Chromatography–Mass Spectrometry

Abundance C3-Alkylbenzenes
(ion 105)

500 000

C4-Alkylbenzenes
300 000 (ion 119)

100 000
0

200 000 C1-Indanes

(ion 117)

100 000

40 000 C2-Indanes
(ion 131)
20 000

200 000
C1-Naphthalenes
(ion 142)
100 000

15 000 C2-Naphthalenes
(ion 156)
10 000

5000

0
6 7 8 9 10 Time

Carbon # 9 10 11 12 13 14 15

Figure 4 Example of extracted ion chromatograms from a 75% evaporated gasoline sample. One can clearly see the patterns exhibited
by the different ions representative of organic compounds. Reproduced from Stauffer E, Dolan JA, and Newman R (2008) Fire Debris Analysis, p. 317.
Burlington, MA: Elsevier Academic Press. Copyright ã 2008, Elsevier.

In practice, all modern MS exhibit a scan rate high enough
(2–10 Hz) to allow for a good chromatographic resolution.
However, the chromatographic resolution obtained with a
regular GC–MS is definitely lower than that obtained from a
GC-FID for example. The reason is that the FID has a scan rate
of approximately 200 Hz. Actual MS scan rates are not consid-
ered an issue for regular GC–MS; however, they become a
concern with new methods such as two-dimensional compre-
hensive gas chromatography–mass spectrometry (GCGC–MS).
In this case, all the components coming out of the first gas
chromatograph are subjected to a second separation (based on
different characteristics) in another chromatograph. The scan rate
must be of at least 50 Hz, thus allowing for enough MS scans
during the time required for the second separation. This scan
rate can only be achieved with a different MS technology: time-
of-flight mass spectrometry (TOF-MS).
Instrumentation
There are very few variations regarding the gas chromatograph.
All modern chromatographs use a capillary column with a
coated stationary phase, which offers a very high resolution.
The injection techniques, split or splitless, are also available on
all gas instruments.
The main variation found in a GC–MS lies in the MS,
which offers different major alternatives. There are three
types of mass spectrometers available on the market today:

Figure 5 An Agilent 6890N-5975 gas chromatograph–mass
spectrometer. An Agilent 7683B autosampler is present above the GC
on the left. Reproduced from Stauffer E, Dolan JA, and Newman R (2008)
Fire Debris Analysis, p. 246. Burlington, MA: Elsevier Academic Press.
Copyright ã 2008, Elsevier.
quadrupole, ion trap, and TOF. Each presents its advantages
and drawbacks and some are more suitable for some types of
analysis than others. Figure 5 shows a typical GC–MS setup
in a forensic laboratory.
With the computer controlling system and the autosam-
pler, a modern GC–MS is a highly capable instrument that
can guarantee a very high throughput. This provides tremen-
dous relief in terms of the manpower requirement for a
forensic laboratory. The convenience of its use is also an
important factor contributing to its reputation as a gold
standard. Basically, it is possible to fully automate the sepa-
ration of 150 complex mixtures, including the identification
of their analytes. In other words, one can let the instrument
run by itself for several days without worrying about it and
just concentrate on the interpretation of the results.
Forensic Applications
The applications of GC–MS to the forensic field are extremely
diverse. Basically, all analytes that can go through a gas chro-
matograph can be analyzed by GC–MS. So, everything that is
volatile under 300–500  C, does not decompose at these tem-
peratures, and exhibits a molecular weight below 600 amu (up
to 1000 with new MS) can be analyzed by GC–MS. This leaves
room for many different applications, which is the reason why
GC–MS is one of the most versatile analytical instruments that
one can find in a forensic laboratory.
The most common applications in forensic science are the
analysis of fire debris, drugs, explosives, and toxins. Other
applications, less often encountered, include the analysis of
hydrocarbons in environmental crime investigations, vegetable
oil residues, and, when using pyrolysis-GC–MS, paints, fibers,
and plastics.
In fire debris analysis, ignitable liquid residues extracted
from fire debris samples are analyzed in order to detect for
the presence of an ignitable liquid, possibly used as an accel-
erant at a fire scene. These samples consist of complex mixtures
of hydrocarbons, often unresolved. The power of MS is fully
Methods | Gas Chromatography–Mass Spectrometry 601
exploited by using EIC and EIP to interpret the complex chro-
matograms. Because of the type of organic molecules, it is
possible to extract different profiles using several specific ions
and, thus, to facilitate the interpretation of the chromatograms.
Fire debris analysis is mostly concerned with qualitative, maybe
semi-quantitative, analysis.
In drug analysis, the forensic scientist is presented with
unknown samples of powder or liquid and must determine
the nature and quantity of its components. Not all drugs can be
analyzed through GC–MS, given that some are sensitive to
the heat of the injector, for example. However, the analysis
can be carried out on most drugs. With many drugs, such as
cocaine and heroin seized from the street, GC–MS provides a
very thorough analysis. Determining that an active substance
is present and at what quantity is an important element for
the prosecution. However, identifying the adulterants and the
contaminations/impurities also present brings a whole new
edge to the investigation. As a matter of fact, adulterants and
contaminations/impurities are used to perform drug profiling,
a method capable of establishing links between individual
seizures and identifying the drug network. GC–MS is a pri-
mordial tool in this regard, since it allows for a complete
separation and identification of unknowns in a substance.
Because MS is not always optimal in quantitative analysis, it
is often used in conjunction with other detectors, such as FID,
to obtain both qualitative and quantitative accurate results.
In explosive analysis, the goal is to analyze seized sub-
stances or residues of possible explosives. Again, the scientist
not necessarily being aware of the type of substance involved,
GC–MS’s versatility brings a great advantage to the identifica-
tion of explosives and residues. It is considered as a sufficient
technique to allow for the identification of many explosives
without any other testing.
Forensic toxicology is a wide field concerned with the
detection of drugs, metabolites, or toxins in the human body.
This ranges from simple medication to alcohol consumption
and other drug-related substances. The samples are body fluids
such as blood and urine and other body samples, such as hair,
tissues, or fingernails. The separation and identification power
of GC–MS presents an interesting advantage, even though not
all substances can be run through GC–MS. A forensic toxicol-
ogy lab includes many other analytical instruments such as
liquid chromatography, capillary electrophoresis, and immu-
noassay. As such, GC–MS is one important tool among others,
such as liquid chromatography–mass spectrometry (LC–MS),
in a forensic toxicology laboratory.
In environmental crime investigation, one is often con-
fronted with hydrocarbon spills or contaminations. Because
hydrocarbons are extremely complex mixtures of hundreds of
components, the separation power exhibited by GC and the
characterization power of MS are fully necessary. As a matter of
fact, environmental laboratories often use specific parameters,
in terms of separation, that are quite different from parameters
used in traditional forensic settings, because of the complexity
of the substances they are dealing with. The ultimate goal of an
environmental investigation is not to simply demonstrate that
the pollution exists, as one rarely needs a GC–MS for that;
however, it is to identify the source of the pollution. In this
scope, different techniques of oil spill fingerprinting, for exam-
ple, have been developed over the years.
602 Methods | Gas Chromatography–Mass Spectrometry
The analysis of vegetable oils (or rather their derivates) by
GC–MS has been well known for many years in the food industry.
In fire investigation, a method has been developed to recover
vegetable oil residues from a fire that could have been triggered by
the autoignition of oil residues. This method uses GC–MS
to analyze the extract and to identify the type of oil involved.
GC–MS is clearly the best instrument to carry out this type of
analysis, because of its combined separation and analytical
power.
Finally, many other samples can be analyzed by GC–MS.
This is the case with plastics, polymers, paints, and fibers
whose composition can be analyzed after being pyrolyzed.
This provides important information regarding a common
source between a questioned and a comparison samples. In
this regard, pyrolysis-GC–MS was developed, allowing for
the direct injection of pyrolysis products into the GC. This
technique, less often encountered, has also been used for
many years in different crime laboratories around the world.
See also: Chemistry/Trace/Drugs of Abuse: Analysis of
Controlled Substances; Chemistry/Trace/Explosives: Explosives:
Analysis; Chemistry/Trace/Fire Investigation: Analysis of Fire
Debris; Interpretation of Fire Debris Analysis; Methods: Gas
Chromatography; Liquid Chromatography–Mass Spectrometry; Mass
Spectrometry; Toxicology/Drugs of Abuse: Drugs in Hair; Validation
of Twelve Chemical Spot Tests for the Detection of Drugs of Abuse.
Further Reading
Gohlke RS and McLafferty FW (1993) Early gas chromatography/mass spectrometry.
Journal of the American Society for Mass Spectrometry 4: 367–371.
Levine B (ed.) (2010) Principles of Forensic Toxicology, 3rd edn. Washington, DC:
American Association for Clinical Chemistry.
Silverstein RM, Webster FX, and Kiemle D (2005) Spectrometric Identification of
Organic Compounds, 7th edn. Hoboken, NJ: John Wiley and Sons.
Smith FP (ed.) (2005) Handbook of Drug Analysis. Burlington, MA: Elsevier Academic
Press.
Sparkman OD, Penton Z, and Kitson FG (2011) Gas Chromatography and Mass
Spectrometry: A Practical Guide, 2nd edn. Burlington, MA: Elsevier Academic Press.
Stauffer E, Dolan JA, and Newman R (2008) Fire Debris Analysis. Burlington, MA:
Elsevier Academic Press.
Terrettaz-Zufferey AL, Ratle F, Ribaux O, Esseiva P, and Kanevski M (2007) Pattern
detection in forensic case data using graph theory: Application to heroin cutting
agents. Forensic Science International 167: 242–246.
Wang Z and Stout S (2006) Oil Spill Environmental Forensics: Fingerprinting and
Source Identification. Burlington, MA: Elsevier Academic Press.
Wong RC and Tse HY (eds.) (2005) Drugs of Abuse: Body Fluid Testing. Totowa, NJ:
Humana Press.
Yinon J and Zitrin S (1996) Modern Methods and Applications in Analysis of
Explosives. Hoboken, NJ: John Wiley and Sons.
Zoro JA and Hadley K (1976) Organic mass spectrometry in forensic science. Journal of
the Forensic Science Society 16(2): 103–114.
Relevant Websites
http://www.agilent.com – Agilent
http://www.perkinelmer.com – PerkinElmer Inc.
http://www.restek.com – Restek Corporation