Gas chromatography (GC) is an essential analytical technique in pharmaceutical analysis, used for separation, identification, and quantitation of volatile and semi-volatile compounds. This introduction covers GC theory — retention time, partitioning, adsorption, capacity factor (k’), plate theory (HETP, number of theoretical plates) and the Van Deemter relationship — and instrumentation — injector types, capillary and packed columns, stationary phases, carrier gases, oven temperature programming, and detectors like FID, TCD and MS. Key concepts also include sample preparation, split/splitless injection, resolution, selectivity and quantitative methods such as calibration and internal standards. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What property of analytes primarily determines their separation in gas chromatography?
- Polarity of the detector
- Interaction with the stationary phase
- Size of the sample injector
- Detector response time
Correct Answer: Interaction with the stationary phase
Q2. Which carrier gas is commonly used for high-sensitivity Flame Ionization Detector (FID) applications?
- Carbon dioxide
- Helium
- Nitrogen
- Oxygen
Correct Answer: Helium
Q3. What does retention time (tR) represent in GC?
- The time a detector takes to respond
- The time between injection and detector signal peak
- The time to replace the carrier gas
- The time required for column conditioning
Correct Answer: The time between injection and detector signal peak
Q4. Which detector is most selective for halogenated compounds and used for trace analysis?
- Flame Ionization Detector (FID)
- Thermal Conductivity Detector (TCD)
- Electron Capture Detector (ECD)
- Nitrogen-Phosphorus Detector (NPD)
Correct Answer: Electron Capture Detector (ECD)
Q5. The Van Deemter equation describes the relationship between:
- Retention time and detector sensitivity
- Column efficiency (HETP) and linear velocity
- Carrier gas purity and baseline noise
- Injector temperature and sample loss
Correct Answer: Column efficiency (HETP) and linear velocity
Q6. What is a major advantage of capillary columns over packed columns?
- Lower resolution
- Higher capacity for large sample loads
- Higher separation efficiency and resolution
- Less need for carrier gas
Correct Answer: Higher separation efficiency and resolution
Q7. In split injection, why is a portion of the vaporized sample vented?
- To increase detector noise
- To prevent column overload and improve peak shape
- To cool the inlet rapidly
- To change the stationary phase polarity
Correct Answer: To prevent column overload and improve peak shape
Q8. What does the capacity factor (k’) indicate?
- Detector linear range
- Relative retention of an analyte compared to dead time
- Column temperature stability
- Injector split ratio
Correct Answer: Relative retention of an analyte compared to dead time
Q9. Which detector measures changes in thermal conductivity of the gas stream?
- FID
- TCD
- ECD
- NPD
Correct Answer: TCD
Q10. Which parameter directly improves resolution between two adjacent peaks?
- Decreasing column length
- Increasing selectivity (α) or plate number (N)
- Using a lower purity carrier gas
- Decreasing detector sensitivity
Correct Answer: Increasing selectivity (α) or plate number (N)
Q11. What is the primary role of the GC oven?
- To detect eluted compounds
- To maintain and program column temperature for optimal separation
- To vaporize the sample
- To provide carrier gas flow
Correct Answer: To maintain and program column temperature for optimal separation
Q12. Kovats retention index is used to:
- Quantify analyte concentration
- Standardize retention times across different columns and conditions
- Measure detector baseline noise
- Set injector split ratio
Correct Answer: Standardize retention times across different columns and conditions
Q13. Which stationary phase is most suitable for separating nonpolar hydrocarbons?
- Highly polar polyethylene glycol
- Nonpolar dimethylpolysiloxane
- Polar cyano phase
- Strong anion exchange
Correct Answer: Nonpolar dimethylpolysiloxane
Q14. What is the effect of increasing column temperature on retention times?
- Retention times generally increase
- Retention times generally decrease
- Retention times remain unchanged
- Retention times fluctuate randomly
Correct Answer: Retention times generally decrease
Q15. Which detector is nearly universal but less sensitive than FID and often used for permanent gases?
- ECD
- TCD
- NPD
- SCD (Sulfur Chemiluminescence Detector)
Correct Answer: TCD
Q16. How does a Flame Ionization Detector (FID) detect analytes?
- By measuring change in thermal conductivity
- By ionizing organic compounds in a flame and measuring current
- By capturing electrons from electronegative compounds
- By measuring mass-to-charge ratios
Correct Answer: By ionizing organic compounds in a flame and measuring current
Q17. What is splitless injection primarily used for?
- Analyzing very volatile gases only
- Trace analysis when sample concentration is low
- To decrease detector sensitivity
- To improve column lifetime
Correct Answer: Trace analysis when sample concentration is low
Q18. Which factor does NOT influence the number of theoretical plates (N)?
- Column length
- Mobile phase linear velocity
- Detector type
- Stationary phase efficiency
Correct Answer: Detector type
Q19. GC-MS coupling provides which major advantage?
- Reduced separation efficiency
- Direct mass spectral identification of eluted compounds
- Elimination of carrier gas
- Higher sample capacity than LC-MS
Correct Answer: Direct mass spectral identification of eluted compounds
Q20. Which sample property makes a compound unsuitable for GC analysis?
- High volatility
- Very high molecular weight and thermal instability
- Low polarity
- Moderate boiling point
Correct Answer: Very high molecular weight and thermal instability
Q21. Which procedure reduces contamination and prolongs column life?
- Overloading the column
- Using guard columns or retention gap
- Using impure carrier gas
- Running very high split ratios always
Correct Answer: Using guard columns or retention gap
Q22. What does resolution (Rs) between two peaks depend on?
- Only retention times
- Retention factor (k’), selectivity (α), and efficiency (N)
- Detector manufacturer
- Injector color
Correct Answer: Retention factor (k’), selectivity (α), and efficiency (N)
Q23. Which carrier gas offers highest optimal linear velocity for best efficiency according to Van Deemter?
- Nitrogen
- Helium
- Carbon dioxide
- Argon
Correct Answer: Helium
Q24. In pharmaceutical GC quantitation, why is an internal standard used?
- To change stationary phase polarity
- To correct for injection variability and matrix effects
- To reduce detector sensitivity
- To speed up oven programming
Correct Answer: To correct for injection variability and matrix effects
Q25. Temperature programming in GC is beneficial because it:
- Makes all peaks elute at the same time
- Improves analysis of mixtures with wide boiling point ranges
- Prevents any interaction with the stationary phase
- Eliminates need for carrier gas
Correct Answer: Improves analysis of mixtures with wide boiling point ranges
Q26. What is the main principle of an Electron Capture Detector (ECD)?
- Measuring mass spectra
- Detecting compounds that capture electrons, reducing current
- Measuring flame ionization current
- Detecting thermal conductivity changes
Correct Answer: Detecting compounds that capture electrons, reducing current
Q27. Which maintenance issue most likely causes peak tailing in GC?
- Column perfectly deactivated
- Active sites in the inlet or column due to contamination
- Using helium as carrier gas
- Too narrow a split ratio
Correct Answer: Active sites in the inlet or column due to contamination
Q28. Headspace GC is especially suitable for analyzing:
- Non-volatile polymers
- Volatile organic compounds from solids or liquids without direct injection
- High-boiling triglycerides
- Metals
Correct Answer: Volatile organic compounds from solids or liquids without direct injection
Q29. The nitrogen-phosphorus detector (NPD) is selective for:
- Hydrocarbons only
- Nitrogen- and phosphorus-containing compounds
- Inorganic gases like CO2
- All electronegative compounds
Correct Answer: Nitrogen- and phosphorus-containing compounds
Q30. Which practice improves quantitative accuracy in GC calibration?
- Using single-point external calibration without replication
- Using multi-point calibration and quality control standards
- Not using any standards and relying on retention time only
- Changing detector type between calibrations
Correct Answer: Using multi-point calibration and quality control standards

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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