Principle of gas chromatography MCQs With Answer

Principle of Gas Chromatography MCQs With Answer

This quiz set is designed for M.Pharm students preparing for Advanced Instrumental Analysis (MPA 201T). It focuses on the principles and practical aspects of gas chromatography (GC), covering fundamental theory (retention mechanisms, partitioning, Van Deemter), instrumentation (columns, injectors, detectors), operational modes (split/splitless, temperature programming, headspace), and hyphenated techniques (GC–MS). Questions emphasize understanding of column behavior, detector selection, quantitation strategies, method development and troubleshooting common issues such as peak tailing, carryover and thermal degradation. Use these MCQs to test and deepen conceptual knowledge, sharpen problem-solving skills in chromatographic method design, and prepare for exams and laboratory applications.

Q1. Which retention mechanism is primarily responsible for separation in conventional capillary gas chromatography with a non-polar stationary phase?

• Ion-exchange interaction between analyte ions and the stationary phase
• Partitioning of analytes between the mobile gas phase and the liquid stationary phase
• Covalent bonding of analytes to the stationary phase
• Size-exclusion based on molecular dimensions

Correct Answer: Partitioning of analytes between the mobile gas phase and the liquid stationary phase

Q2. In the Van Deemter equation, which term describes the contribution of longitudinal diffusion to band broadening in GC?

• The A term (eddy diffusion)
• The B term, proportional to 1/linear velocity
• The C term, proportional to linear velocity
• The D term representing stationary phase film thickness

Correct Answer: The B term, proportional to 1/linear velocity

Q3. What is the main analytical advantage of using temperature programming in GC?

• To increase detector sensitivity for all compounds uniformly
• To immobilize volatile analytes on the stationary phase
• To sharpen peaks of very volatile compounds only
• To separate analytes with a wide range of volatilities in a single run

Correct Answer: To separate analytes with a wide range of volatilities in a single run

Q4. Which detector provides near-universal response for organic compounds and is highly compatible with GC–MS interfaces?

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

Correct Answer: Flame ionization detector (FID)

Q5. In splitless injection, the main purpose is to:

• Introduce a small fraction of the sample to avoid overloading
• Maximize sample transfer of trace analytes onto the column
• Prevent degradation of thermally labile compounds by rapid cooling
• Allow simultaneous introduction of solvent and sample into separate columns

Correct Answer: Maximize sample transfer of trace analytes onto the column

Q6. Which stationary phase property most strongly influences selectivity between isomers in GC?

• Column inner diameter
• Polarity and chemical functionality of the stationary phase
• Carrier gas purity
• Injector liner volume

Correct Answer: Polarity and chemical functionality of the stationary phase

Q7. What is the primary reason for deactivating inlet liners and column surfaces when analyzing active pharmaceutical compounds?

• To reduce column bleeding at high temperatures
• To minimize analyte adsorption and secondary interactions
• To improve carrier gas flow stability
• To enhance the thermal conductivity of the inlet

Correct Answer: To minimize analyte adsorption and secondary interactions

Q8. Which column type is most appropriate for high-resolution separation of volatile small molecules in pharmaceutical analysis?

• Packed column with porous polymer packing
• Wide-bore capillary column (>0.53 mm ID)
• Wall-coated open tubular (WCOT) capillary column with thin film
• Ion-exchange packed column

Correct Answer: Wall-coated open tubular (WCOT) capillary column with thin film

Q9. Which equation defines chromatographic resolution (R_s) between two adjacent peaks?

• R_s = (t_R2 – t_R1) / (w_1/2 average)
• R_s = (t_R2 + t_R1) / (w_1 + w_2)
• R_s = (t_R2 – t_R1) / 0.5(w_1 + w_2)
• R_s = (HETP) / (number of theoretical plates)

Correct Answer: R_s = (t_R2 – t_R1) / 0.5(w_1 + w_2)

Q10. Electron capture detectors (ECD) are particularly sensitive to which class of compounds common in pharmaceutical impurity profiling?

• Nonpolar hydrocarbons
• Halogenated compounds (e.g., chlorinated impurities)
• Alkali metal salts
• Monoterpenes

Correct Answer: Halogenated compounds (e.g., chlorinated impurities)

Q11. In GC–MS the process of chemical ionization (CI) differs from electron ionization (EI) primarily by:

• Producing more extensive fragmentation than EI
• Using a reagent gas to generate protonated (or adduct) molecular ions with less fragmentation
• Incompatibility with capillary columns due to high pressure
• Requiring ultraviolet radiation instead of electrons

Correct Answer: Using a reagent gas to generate protonated (or adduct) molecular ions with less fragmentation

Q12. Which operational change most directly decreases plate height (H) and improves efficiency in a GC column?

• Increasing column temperature while holding flow constant for all analytes
• Choosing an optimal linear velocity near the Van Deemter minimum
• Doubling film thickness regardless of analyte volatility
• Switching from helium to air as carrier gas

Correct Answer: Choosing an optimal linear velocity near the Van Deemter minimum

Q13. What is the major concern when analyzing thermally labile drug substances by GC and how is it commonly addressed?

• Excessive column bleed — addressed by lowering carrier gas flow
• Thermal degradation — addressed by derivatization or using lower inlet/column temperatures (e.g., PTV injection)
• Detector saturation — addressed by increasing split ratio permanently
• Loss of volatility — addressed by increasing detector temperature

Correct Answer: Thermal degradation — addressed by derivatization or using lower inlet/column temperatures (e.g., PTV injection)

Q14. Which carrier gas is most commonly recommended for maximum sensitivity and compatibility with mass spectrometry detection in GC?

• Nitrogen, because it is cheapest
• Hydrogen, because it gives highest thermal conductivity
• Helium, because of optimal diffusion properties and inertness with MS
• Carbon dioxide, because it increases retention times

Correct Answer: Helium, because of optimal diffusion properties and inertness with MS

Q15. In quantitation by GC, the internal standard method is preferred over external standard when:

• Analyte response is perfectly stable and identical to standard
• Sample injection and matrix effects cause variable recovery or response
• Only a single calibration point is available and instrument is perfectly precise
• Using detectors that give absolute molar response independent of structure

Correct Answer: Sample injection and matrix effects cause variable recovery or response

Q16. What is column bleed and why is it important to minimize in high-sensitivity GC–MS analyses?

• Bleed is loss of carrier gas through fittings — it has no effect on MS background
• Bleed is degradation of analyte at the injector — it increases retention times
• Bleed is release of stationary phase components at high temperatures — it increases background noise and contaminates MS spectra
• Bleed is leakage of sample through the septum — it reduces sample volume delivered

Correct Answer: Bleed is release of stationary phase components at high temperatures — it increases background noise and contaminates MS spectra

Q17. Which sample introduction technique is most suitable for analyzing volatile residual solvents in pharmaceuticals?

• Large-volume splitless injection of neat API solution
• Headspace GC, especially static or dynamic headspace sampling
• Direct syringe injection of solid dosage form into the column
• Pyrolysis GC to thermally fragment the dosage form

Correct Answer: Headspace GC, especially static or dynamic headspace sampling

Q18. In capillary GC, increasing stationary phase film thickness will typically:

• Decrease retention for polar analytes and reduce resolution
• Increase retention for volatile analytes and improve capacity for late-eluting compounds
• Eliminate the need for temperature programming entirely
• Reduce column bleed at very high temperatures

Correct Answer: Increase retention for volatile analytes and improve capacity for late-eluting compounds

Q19. Which troubleshooting step is most appropriate if peaks show consistent fronting (leading edge distortion) in a GC analysis?

• Check for column overload, reduce injection quantity or lower sample concentration
• Increase oven temperature ramp rate immediately
• Replace detector with one of lower sensitivity
• Increase split ratio to concentrate the column

Correct Answer: Check for column overload, reduce injection quantity or lower sample concentration

Q20. Which of the following column stationary phase descriptions is most suited for separating structurally similar polar drug metabolites (e.g., hydroxylated isomers)?

• Non-polar dimethyl polysiloxane phase
• Strongly polar polyethylene glycol (PEG) or cyanopropylphenyl-modified phase
• Inert deactivated fused silica with no bonded phase
• Porous polymer packing designed for gas adsorption separations

Correct Answer: Strongly polar polyethylene glycol (PEG) or cyanopropylphenyl-modified phase

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