Gas chromatography-mass spectrometry (GC-MS) combines the separation capabilities of gas chromatography with the mass analysis capabilities of mass spectrometry. It allows unknown substances to be separated, quantified, and identified. The document discusses the principles and components of GC and GC-MS, including sample introduction, columns, detectors, interfaces between GC and MS, ionization methods in MS, and interpretation of chromatograms and spectra. GC separates components which are then analyzed by MS to produce a 3D graph allowing identification of each separated component.

1. Gas Chromatography
& GC-MS
submitted by: Submitted To:
Himanshu Sachdeva Dr. Rakesh kr.
Marwaha
Roll no.1705 Assistant Professor
Dptt. Of Pharmaceutical Sc. MDU, Rohtak1

2. Contents:
 Introduction to GC
 Types of GC and Principles
 Instrumentation of GC
 Derivatisation
 Applications of GC
 Introduction to GC-MS
 Interfaces used in GC-MS
 Interpretation
 Application
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3. GAS CHROMATOGRAPHY
• Gas chromatography (GC) is a common type of
chromatography used in analytical chemistry for
separating and analyzing compounds that can be
vaporized without decomposition.
• The development of GC as an analytical technique
was discovered by Martin and Synge 1941
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4. Gas Chromatography:
• Gas Solid Chromatography (GSC)
• Gas Liquid Chromatography (GLC)
In both cases, gas is used as mobile phase and
solid and liquid is used as stationary phase
respectively.
Gas Solid Chromatography: is not widely used
because limited no of stationary phase
available. GSC is used only in case, where there
is a less solubility of solutes in stationary phase
Principle of separation is ADSORPTION
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5. GAS Liquid Chromatography:
Principle:
The principle of separation in GLC is PARTITION. Gas is
used as mobile phase and liquid which is coated on a
solid support is used as a stationary phase.
The mixture of components to be separated is
converted to vapour and mixed with gaseous mobile
phase . The component which is more soluble in
stationary phase travel slower and eluted later and
the components which are less soluble travel faster
and eluted first. Hence the components are
separated according to their partition co-efficient.
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6. CRITERIA FOR GLC:
1.Volatility: Unless a compound is volatile, it can
not be mixed with mobile phase. So can not be
separate out.
2.Thermostability: The compounds which are in
solid or liquid form, first need to be converted to
gaseous form so they have to be heated to a
higher temperature. At that temperature, the
compound have to be thermostable.
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7. GAS CHROMATOGRAPHIC APPARTUS
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8. PRACTICAL REQUIREMENTS
• Carrier gas
• Flow regulator and flow meter
• Injection devices
• Columns
• Temperature control device
• Detectors
• Recorders and Integrators
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9. CARRIER GAS:
• The choice of carrier gas determines the
efficacy of chromatographic separation.
Most widely used are hydrogen, helium,
nitrogen and argon.
• The gas must be inert, less expensive,
suitable for detector, high purity, should
not cause the risk of fire.
• As carrier gas is compressible, gases are
stored under high pressure in cylinder and
used when required.
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10. Flow Regulators:
As carrier gas are stored under high pressure,
flow regulators are used to deliver the gas with
uniform pressure or flow rate. Flow meter are
used to measure the flow rate of carrier gas
Eg.
Rotameter
Soap bubble
meter
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11. Sample Introduction
• The sample is usually introduced in form of
solution (~0.5 ml) into the injector
• Injector has dual role, provides an inlet for the
sample and vaporizes the sample and mixes it with
mobile phase
• Modes of injection vary according to their types
• Direct Vaporisation injector
• Cold On-Column Injector
• Split/Splitless Injector
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12. 12
Direct vaporization injection
In direct flash vaporization
injection, a liquid sample is
injected via a syringe into a
heated injection port. The
sample is rapidly vaporized in the
injection port, then transferred to
the column

13. Cold on-column injection
•The sample is injected directly on column and
vaporisation occurs after the injection
•Needle penetrates the column or precolumn kept at
4o
C before raising it to normal operating temperature
•Useful for thermolabile
components
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14. • It is designed to maintain the constant flow of carrier
gas and to control the amount of sample enters into
the column
• If the split vent is closed, via a computer-controlled
split valve, then all of the sample introduced into the
injector vaporizes and goes on (into) the
column(splitless mode). If the split vent is open then
most of the vaporized sample is thrown away to waste
via the split vent and only a small portion of the sample
is introduced to the column.(split mode)
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GC – Split/Splitless Injections

15. GC – Split/Splitless Injections
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16. Temperature Control Device
Repeaters: Are used in GC to concert the sample into
vapour form and mix with mobile phase
Thermostatically controlled oven: Since partition
coefficient as well as solubility of a solute depends
upon temperature, temp. maintaining in a column is
highly essential for efficient separation
• Isothermal programming
• Linear programming
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17. COLUMNS
Column is one of the important part of GC
which decides the separation efficiency.
Columns are made up of glass and stainless
steel.
Classification of columns:
Depending on its use:
• Analytical column
• Preparative column
Depending on its nature:
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18. Column – Types
Packed column: Are available in packed manner
commercially and hence are called as Packed
column. Different columns ranging from non polar
to polar are available.
Open tubular/ Capillary Column: They are made
up of long capillary tubing of 30-90 meters in
length and have diameter of 0.025 to 0.075 cm.
These are made up of stainless steel and are in the
form of a coil. The inner wall of the capillary is
coated with stationary phase liquid in the form of
a thin film.
More sample can not be loaded
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19. Support Coated Open Tubular Column: these
columns are made by depositing a micron size
layer of support material on the inner wall of
the capillary column and then coated with a
thin film of liquid phase.
These columns also have low resistance to flow
of carrier gas but offers the advantage of more
sample load or capacity.
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20. GC – Detectors
Detectors are most important part of GC instrument
Properties of a good detector:
• Applicable to wide range of sample
• High sensitivity to even small concentration
• Rapidity of response
• Linearity
• Non destructive to sample
• Simple and easy to maintain
TYPES OF DETECTOR
• Thermal conductivity detector
• Flame ionisation detector
• Electron Capture Detector 20

21. Flame Ionization Detector (FID)
The carrier gas used with this type of detector
can be hydrogen.
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22. Thermal Conductivity Detector (TCD)
The principle is based upon the thermal conductivity
difference between carrier gas and sample components. TCD
has two platinum wire of uniform dimension which form a
Wheatstone bridge
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23. Electron Capture Detector (ECD)
The ECD has two electrodes. One of the electrode is
treated with a radioactive isotope which emits e- as it
decays(anode)
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24. Recorders: are used to record the responses
obtained from detector after amplfication. They
record the baseline and all the peaks obtained
with respect to time.
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25. Derivatisation of sample:
It is a technique of treatment of the sample to
improve the process of separation by column or
detection by detector.
Precolumn derivatisation: this is done to
improve some properties of the sample for
separation by column. By this technique, the
components are converted to more volatile and
thermostable derivative. Moreover improved
separation and less tailing will be seen after such
treatment. eg. Silylation, acylation and alkylation.
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27. • Postcolumn derivatisation: It is done to
improve the response shown by detector. The
components may not be detected by detector
unless derivatisation is done. The component
may be converted in such a way that their
ionisation or affinity toward electron is
increased.
eg. Tagging with chlorine can improve
response on an ECD detector.
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28. Application Of GC:
• Qualitative analysis
• Checking the purity of a compound
• Presence of impurity
• Quantitative analysis
• Isolation of drug or metabolites in urine
• Speed – very fast, minutes
• Sensitivity – high sensitivity, (ppm range)
• Simplicity – simple to operate and understand
• Resolution – high resolution of closely related
compounds
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30. GC-MS
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31. GC-MS
• GC-MS is an advance analytical
instrumental technique that combines the
physical separation capability of GC with
the mass analysing capability of MS.
• Gas chromatography coupled with mass
spectrometry is a versatile tool to separate,
quantify and identify unknown substances.
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32. Gas Chromatography-Mass Spectrometry
(GC-MS)
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33. COUPLING OF GC TO MS
• output of the GC must be reduced to vacuum of
10-5
to 10-6
atm The interface b/w GC-MS play an
important role in the overall efficiency of
instrument
• Both system are heated at 200-300⁰C, both deal
with compound in vapor state.
• Only one problem is that the atmospheric pressure
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34. Types of Interfaces: there are four types of
interfaces available. These are-
• JET SEPREATOR
• PERMSELECTIVE MEMBERANE
• MOLECULAR EFFUSION
• DIRECT INTRODUCTION
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35. JET SEPARATOR: In these separators, the GC flow is
introduced into an evacuated chamber through a
restricted capillary. Light particle dispersed away
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36. Permselective membrane interface: it is made of a
silicone-rubber membrane that transmits organic
non-polar molecules
and acts as a barrier for (non-organic) carrier gases.
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37. The molecular effusion /Watson-Biemann
interface: is based on the molecular filtering of the gas
effluent by means of a porous glass fritted tube.
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38. DIRECT INTRODUCTION: In this method
capillary column is directly inserted into MS
ionisation chamber
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39. Mass Spectrometry
Sample Introduction → Ionization →
Mass Analysis → Ion Detection/Data Analysis
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40. Ionization
• Electron Impact (EI)
• Chemical Ionization (CI)
• Field Desorption (FD)
• Fast Atom Bombardment (FAB)
• Laser Desorption (LD)
• Electrospray Ionization (ESI)
• Matrix Assisted Laser Desorption (MALDI)
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41. Interpretation of Result:
Through GC a CHROMATOGRAM is obtained
Through MS a SPECTRUM is obtained
GC-MS gives a 3D graph which has both chromatogram
and spectrum to each separated components in the
chromatogram.
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42. Chromatogram generated by GC
 While the instrument run, the
computer generated a graph from
signal called chromatogram
 X-axis show the RT
 Y-axis show the intensity of the
signal
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43. Mass Spectrum
• The computer record a graph
for each scan called spectrum
• The mass spectrum is
essentially a fingerprint for the
molecule and can be used to
identify the compound.
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45. Application of GC-MS
Environmental monitoring and clean up
Criminal Forensic
Law enforcement
anti doping test
Food, beverages, and perfume analysis
medicines
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46. Conclusion:
• Gas chromatography coupled with mass
spectrometry is a versatile tool to separate,
quantify and identify unknown substances.
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47. References:
 Braun.R, Introduction To Instrumental Analysis,
Second Edition, PharmaMed Press, Hyderabad, Page
no. 251-270.
 Chatwal.G.R , Anand .S.K, Instrumental method Of
Chemical Analysis, Himalaya Publishing House, Fifth
Edition-2012, New Delhi, Page no. 420-449.
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