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matrices such as blood, urine, and feces with the
aim of detecting, identifying, and quantifying as
many metabolites as possible. As the concentra-
tion and composition of the metabolome re
The comparison of GC/MS with other analytical
techniques like LC/MS and NMR with
respect to their individual strengths, limita-
tions, and applications has also been exten-
sively reviewed.
9
e
15
As there are many
excellent accounts on the principles of GC/MS
technique, applications, advantages, and limi-
tations, these topics are not covered in the
current chapter.
In recent years, metabonomics has evolved
signi
ect
the host phenotype (e.g., age, gender, and health
status), and external stimuli related to drug, diet,
and gut microbiome,
3
the effects of extra-
genomics factors pertaining to diseases, drug effi-
-
cacy, or toxicity could be investigated.
Metabolites are downstream end products of
transcription and translation processes and are
known to regulate gene expression and function
as building blocks for biosynthesis of more
complex chemical molecules. Unlike DNA,
RNA, and proteins that are made up of chemi-
cally well-de
cantly in terms of scale and complexity.
One example is the Human Serum Metabolome
(HUSERMET) project in which thousands of
clinical samples were analyzed (
http://www
.husermet.org
)
. In other projects, the large-scale
temporal dynamics of metabolic perturbation
in biological systems were monitored.
16
e
18
Such large-scale studies stress the limits of the
GC/MS technique as well as the subsequent
data processing methods. In this chapter, an
overview of GC/MS-based metabonomics in
biomarker discovery is provided, followed by
examples of
ned building blocks, metabolites
show great chemical diversity. In addition to
the diverse chemical properties, the large
number of molecules (ranging from hundreds
to thousands of metabolites) constituting the
metabolome and the wide dynamic range of
metabolite
cant
analytical challenges in metabonomics. Various
analytical techniques such as gas chromatogra-
phy
e
mass spectrometry (GC/MS), liquid chro-
matography
e
mass spectrometry (LC/MS), and
nuclear magnetic resonance (NMR) spectros-
copy have been used in metabonomics, but no
single analytical provides a complete coverage
of all metabolite classes or resolves the metabo-
lites completely in the complex biological
matrices. Among the various analytical tech-
niques, GC/MS has been demonstrated to
provide high sensitivity, peak resolution, and
reproducibility to meet the requirements of
metabonomics.
4
The availability of GC/MS elec-
tron impact (EI) spectral library facilitates identi-
concentrations
pose
signi
its
application in biomarker
discovery.
c strategies to
address large-scale GC/MS-based metabono-
mics are illustrated.
Importantly, speci
GC/MS IN METABONOMIC
S
Overview of GC/MS-Based
Metabonomics
GC is an excellent separation technique that
resolves analytes chromatographically based
on their volatility and polarity. MS detects
theionsandgeneratesmassspectrumfor
each analyte, and this structural information
aids
fication of biomarkers and further enhances its
applicability in metabonomics.
The instrumentation and principles behind
GC/MS have been discussed in numerous publi-
cations.
5,6
Pasikanti et al.,
4
Fancy et al.
7
and
Garcia et al.
8
provided good overview on GC/
MS-based metabonomics and discussed labora-
tory techniques adopted in metabonomics.
cation. The synergistic
coupling of GC and MS renders the tandem
technique a major analytical workhorse in
metabonomics.
In this section, different aspects of GC/MS-
based metabonomics are discussed based on
the work
in its
identi
ow, as shown in
Figure 1
.
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