Principle and application of gas chromatography MCQs With Answer

Principle and application of gas chromatography MCQs With Answer

Gas chromatography (GC) is a cornerstone technique in Modern Pharmaceutical Analytical Techniques for analyzing volatile and semi-volatile compounds with high sensitivity and selectivity. This curated set of MCQs is designed for M. Pharm students to reinforce core principles of GC, including partitioning mechanisms, column technologies, carrier gas selection, temperature and pressure programming, and quantitation strategies. It also emphasizes applications such as residual solvent testing (ICH Q3C), impurity profiling, essential oils, and GC–MS identification. You will find questions spanning detectors (FID, TCD, ECD, NPD, MS), injection modes (split/splitless, on-column, headspace), stationary phase selection, and performance metrics (k′, N, Rs, van Deemter). Use these MCQs to assess understanding and build confidence for research and quality control tasks.

Q1. GC separation in gas–liquid chromatography primarily relies on which fundamental principle?

• Differential partitioning between the mobile gas and an immobilized liquid stationary phase
• Ion-exchange between mobile phase ions and charged stationary sites
• Distribution between two immiscible liquid phases under high pressure
• Size-exclusion based on molecular hydrodynamic volume

Correct Answer: Differential partitioning between the mobile gas and an immobilized liquid stationary phase

Q2. In a wall-coated open tubular (WCOT) capillary column, the stationary phase is best described as:

• A thin film of liquid phase chemically bonded or coated to the inner wall of the capillary
• Solid adsorbent packed uniformly along the column length
• Liquid stationary phase immobilized on diatomaceous earth support in a 2–4 mm i.d. tube
• Polymer gel matrix crosslinked throughout the column

Correct Answer: A thin film of liquid phase chemically bonded or coated to the inner wall of the capillary

Q3. Which carrier gas allows the highest optimum linear velocity (fast analysis with good efficiency) according to the van Deemter profile?

• Hydrogen (H₂)
• Helium (He)
• Nitrogen (N₂)
• Carbon dioxide (CO₂)

Correct Answer: Hydrogen (H₂)

Q4. For halogenated and other electronegative compounds at trace levels, the most sensitive GC detector is the:

• Electron capture detector (ECD)
• Flame ionization detector (FID)
• Thermal conductivity detector (TCD)
• Flame photometric detector (FPD)

Correct Answer: Electron capture detector (ECD)

Q5. Which sample type is generally NOT suitable for direct GC analysis without prior derivatization or special techniques?

• Highly non-volatile, thermally labile compounds without derivatization
• Volatile organic solvents with low boiling points
• Essential oil components
• Permanent gases and light hydrocarbons

Correct Answer: Highly non-volatile, thermally labile compounds without derivatization

Q6. For trace-level analytes in a high-boiling solvent, which injection technique is preferred to maximize sensitivity?

• Splitless injection with solvent focusing
• Split injection with a high split ratio (e.g., 1:100)
• On-column injection with large volume without focusing
• Programmed temperature vaporization in split mode

Correct Answer: Splitless injection with solvent focusing

Q7. In pharmaceutical QC, headspace GC is most appropriate for:

• Determination of residual solvents per ICH Q3C
• Assay of non-volatile API by GC–FID
• Determination of metal ions in dosage forms
• Measurement of peptide impurities

Correct Answer: Determination of residual solvents per ICH Q3C

Q8. Temperature programming in GC is primarily used because it:

• Improves separation of both early- and late-eluting compounds in complex mixtures within reasonable time
• Decreases column efficiency compared to isothermal runs
• Eliminates the need for carrier gas
• Prevents all forms of column bleed

Correct Answer: Improves separation of both early- and late-eluting compounds in complex mixtures within reasonable time

Q9. The capacity factor (k′) in GC is defined by which expression?

• (tR − tM) / tM
• tM / (tR − tM)
• tR / tM
• (tR1 − tR2) / w

Correct Answer: (tR − tM) / tM

Q10. The main advantage of using an internal standard in GC quantitation is that it:

• Compensates for variations in injection volume and sample preparation
• Eliminates the need for calibration
• Increases detector sensitivity by an order of magnitude
• Reduces column backpressure automatically

Correct Answer: Compensates for variations in injection volume and sample preparation

Q11. For separating polar analytes such as short-chain alcohols and glycols, a recommended stationary phase is:

• Polyethylene glycol (e.g., Carbowax 20M) polar phase
• 100% dimethylpolysiloxane non-polar phase
• Alumina PLOT column for hydrocarbons
• Molecular sieve 5A PLOT for permanent gases

Correct Answer: Polyethylene glycol (e.g., Carbowax 20M) polar phase

Q12. Which statement about the flame ionization detector (FID) is TRUE?

• It has a very wide linear dynamic range and is insensitive to water and inorganic gases
• It is non-destructive and universal for all compounds
• It exhibits the highest sensitivity for halogenated molecules
• It directly provides structural identification

Correct Answer: It has a very wide linear dynamic range and is insensitive to water and inorganic gases

Q13. Which is a correct characteristic of the thermal conductivity detector (TCD)?

• Responds to changes in thermal conductivity and is non-destructive but less sensitive than FID
• Selectively detects nitrogen- and phosphorus-containing compounds
• Requires a hydrogen/air flame for operation
• Cannot be used with helium carrier gas

Correct Answer: Responds to changes in thermal conductivity and is non-destructive but less sensitive than FID

Q14. In GC–MS, a rising baseline at high oven temperatures due to “column bleed” is primarily caused by:

• Thermal degradation of stationary phase at elevated oven temperatures
• Excessive injection volume overloading the column
• Incorrect ionization energy in the MS source
• Using headspace sampling instead of liquid injection

Correct Answer: Thermal degradation of stationary phase at elevated oven temperatures

Q15. The chromatographic resolution (Rs) between two peaks is correctly given by:

• 2(tR2 − tR1) / (w1 + w2)
• (tR2 − tR1) / w
• (tR − tM) / tM
• N = 16(tR/wb)²

Correct Answer: 2(tR2 − tR1) / (w1 + w2)

Q16. Gas–solid chromatography (GSC) is most suitable for the separation of:

• Separation of permanent gases and low-molecular-weight hydrocarbons on porous adsorbents
• Analysis of fatty acid methyl esters
• Separation of steroids on bonded phases
• Determination of residual solvents in drug products

Correct Answer: Separation of permanent gases and low-molecular-weight hydrocarbons on porous adsorbents

Q17. A commonly used silylating reagent to derivatize hydroxyl, carboxyl, and amine groups for GC analysis is:

• N,O-Bis(trimethylsilyl)trifluoroacetamide (BSTFA)
• 2,4-Dinitrophenylhydrazine (DNPH)
• Dansyl chloride
• Trifluoroacetic anhydride (TFAA) in acetonitrile

Correct Answer: N,O-Bis(trimethylsilyl)trifluoroacetamide (BSTFA)

Q18. For GC–MS in electron ionization mode, the preferred carrier gas is:

• Helium because it is inert, efficient, and compatible with MS vacuum systems
• Nitrogen because it gives the lowest van Deemter minimum
• Argon because it enhances ionization efficiency
• Air because it is readily available and inexpensive

Correct Answer: Helium because it is inert, efficient, and compatible with MS vacuum systems

Q19. The area normalization method of GC quantitation assumes that:

• All components elute and have equal detector response factors
• Calibration with an internal standard is unnecessary but response factors differ
• Only the most abundant component needs calibration
• The solvent peak can be used as the internal standard

Correct Answer: All components elute and have equal detector response factors

Q20. A relevant pharmaceutical application of chiral GC is:

• Determining enantiomeric purity of volatile chiral drugs using cyclodextrin-based stationary phases
• Quantifying peptide aggregation
• Measuring inorganic impurities
• Profiling high-molecular-weight polymers without derivatization

Correct Answer: Determining enantiomeric purity of volatile chiral drugs using cyclodextrin-based stationary phases

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