Advantages, limitations and pharmaceutical applications of GC MCQs With Answer

Introduction: Gas chromatography (GC) is a core analytical technique in pharmaceutical analysis, providing high resolution, sensitivity and rapid separation of volatile and semi-volatile compounds. This overview covers the advantages (speed, selectivity, quantitative accuracy, automation), limitations (inability to analyze non‑volatile or thermally labile compounds without derivatization, matrix interferences, limited chiral separation) and key pharmaceutical applications such as residual solvent testing, impurity profiling, stability studies, assay of volatile drugs and GC‑MS for metabolite identification. Practical aspects include column types, detectors (FID, TCD, ECD, MS), sample preparation (headspace, SPME, derivatization) and regulatory validation (ICH Q2). Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary separation principle in gas chromatography?

• Distribution between a mobile gas phase and a stationary liquid/solid phase
• Separation by molecular weight through a membrane
• Electrophoretic mobility under an electric field
• Centrifugal separation based on density differences

Correct Answer: Distribution between a mobile gas phase and a stationary liquid/solid phase

Q2. Which detector is most commonly used for quantifying organic compounds in pharmaceutical GC?

• Mass spectrometer (MS)
• Flame ionization detector (FID)
• Thermal conductivity detector (TCD)
• Electron capture detector (ECD)

Correct Answer: Flame ionization detector (FID)

Q3. Which sample introduction technique is preferred for volatile residual solvents in drug products?

• Direct injection of crude formulation
• Headspace sampling
• Liquid chromatography coupling
• Soxhlet extraction

Correct Answer: Headspace sampling

Q4. A major limitation of GC in pharmaceutical analysis is:

• Inability to separate volatile compounds
• High susceptibility to ion suppression
• Difficulty analyzing non‑volatile or thermally labile compounds without derivatization
• Inapplicability to quantitative work

Correct Answer: Difficulty analyzing non‑volatile or thermally labile compounds without derivatization

Q5. Which of the following improves GC column efficiency (theoretical plates)?

• Using a very wide internal diameter capillary
• Decreasing carrier gas linear velocity to the optimum according to Van Deemter
• Increasing injection volume indefinitely
• Operating at very low column temperature regardless of analyte

Correct Answer: Decreasing carrier gas linear velocity to the optimum according to Van Deemter

Q6. Which detector is most suitable for detecting halogenated impurities at trace levels?

• Flame ionization detector (FID)
• Electron capture detector (ECD)
• Thermal conductivity detector (TCD)
• Refractive index detector (RID)

Correct Answer: Electron capture detector (ECD)

Q7. What is the main advantage of coupling GC with mass spectrometry (GC‑MS) in pharmaceuticals?

• Allows analysis of high molecular weight non‑volatile proteins directly
• Provides structural identification and confirmatory analysis of analytes
• Makes derivatization unnecessary for all compounds
• Eliminates the need for column temperature programming

Correct Answer: Provides structural identification and confirmatory analysis of analytes

Q8. In GC method validation, which parameter assesses the smallest reliably measurable concentration?

• Linearity
• Limit of detection (LOD)
• Ruggedness
• Specificity

Correct Answer: Limit of detection (LOD)

Q9. Which stationary phase is most suitable for separating non‑polar volatile compounds?

• Polar polyethylene glycol (PEG) based phase
• Non‑polar dimethylpolysiloxane phase
• Strong cation exchange phase
• Silica gel with polar functional groups

Correct Answer: Non‑polar dimethylpolysiloxane phase

Q10. Which sample preparation technique concentrates analytes from the headspace onto a fiber for GC analysis?

• Liquid–liquid extraction
• Simplified matrix dilution
• Solid‑phase microextraction (SPME)
• Soxhlet extraction

Correct Answer: Solid‑phase microextraction (SPME)

Q11. For residual solvent analysis per ICH Q3C, which gas chromatographic detector is typically recommended?

• Electron capture detector (ECD)
• Flame ionization detector (FID)
• Refractive index detector (RID)
• UV detector

Correct Answer: Flame ionization detector (FID)

Q12. Which factor most affects retention time in GC?

• Sample color
• Partition coefficient between stationary phase and gas phase
• Detector sensitivity
• pH of the mobile phase

Correct Answer: Partition coefficient between stationary phase and gas phase

Q13. What is the role of derivatization in GC analysis?

• To increase detector noise intentionally
• To make non‑volatile or polar analytes volatile and thermally stable
• To separate enantiomers without chiral columns
• To remove impurities completely from samples

Correct Answer: To make non‑volatile or polar analytes volatile and thermally stable

Q14. Which parameter indicates the degree of separation between two peaks?

• Retention factor (k’)
• Resolution (Rs)
• Capacity factor
• Signal‑to‑noise ratio

Correct Answer: Resolution (Rs)

Q15. In GC, a tailing peak often indicates which problem?

• Excellent column deactivation
• Strong interactions with active sites on stationary phase or inlet
• Excessive carrier gas purity
• Ideal injection technique

Correct Answer: Strong interactions with active sites on stationary phase or inlet

Q16. Which carrier gas provides the highest optimal linear velocity for efficiency in capillary GC using common detectors?

• Nitrogen
• Helium
• Air
• Carbon dioxide

Correct Answer: Helium

Q17. A major benefit of capillary columns over packed columns is:

• Lower resolution but higher sample capacity
• Higher efficiency and resolution with lower sample capacity
• Ability to inject larger volumes without split
• Compatibility with non‑volatile macromolecules

Correct Answer: Higher efficiency and resolution with lower sample capacity

Q18. Which detector is universal and responds to inorganic and permanent gases as well as organics?

• Flame ionization detector (FID)
• Thermal conductivity detector (TCD)
• Electron capture detector (ECD)
• Nitrogen phosphorous detector (NPD)

Correct Answer: Thermal conductivity detector (TCD)

Q19. For chiral separations by GC in pharmaceutical analysis, what is commonly required?

• Standard non‑polar stationary phase
• Chiral stationary phases or chiral derivatization agents
• Higher column temperature only
• Replacement of carrier gas with liquid mobile phase

Correct Answer: Chiral stationary phases or chiral derivatization agents

Q20. Which validation characteristic assesses method reproducibility under varied conditions (different analysts, days)?

• Linearity
• Robustness and intermediate precision (ruggedness)
• Selectivity only
• Limit of quantification exclusively

Correct Answer: Robustness and intermediate precision (ruggedness)

Q21. In GC‑MS, which ionization technique is most widely used for small pharmaceutical molecules?

• Electrospray ionization (ESI)
• Electron ionization (EI)
• Matrix assisted laser desorption ionization (MALDI)
• Atmospheric pressure chemical ionization (APCI)

Correct Answer: Electron ionization (EI)

Q22. What is carryover in GC and why is it problematic?

• A beneficial accumulation of analyte enhancing sensitivity
• Residual analyte remaining in the system that contaminates subsequent runs
• Intentional blending of standards for calibration
• Automated data processing error only

Correct Answer: Residual analyte remaining in the system that contaminates subsequent runs

Q23. Which approach improves quantification accuracy when sample matrix affects analyte response?

• External calibration with solvent standards only
• Standard addition or use of appropriate internal standard
• Increasing injection volume without change in calibration
• Ignoring matrix effects during validation

Correct Answer: Standard addition or use of appropriate internal standard

Q24. In a GC method, what is the purpose of temperature programming?

• To keep column temperature constant for all analytes
• To separate analytes with a wide volatility range more efficiently
• To deactivate the stationary phase continuously
• To reduce detector sensitivity intentionally

Correct Answer: To separate analytes with a wide volatility range more efficiently

Q25. Which of the following is a common hyphenated technique used for confirmatory identification in pharmaceutics?

• GC coupled with ultraviolet detector (GC‑UV)
• GC coupled with mass spectrometry (GC‑MS)
• GC coupled with refractive index detector (GC‑RID)
• GC coupled with centrifugal elution

Correct Answer: GC coupled with mass spectrometry (GC‑MS)

Q26. Which ICH guideline primarily governs validation of chromatographic methods like GC?

• ICH Q3C Residual Solvents
• ICH Q2(R1) Validation of Analytical Procedures
• ICH Q8 Pharmaceutical Development
• ICH M4 Common Technical Document

Correct Answer: ICH Q2(R1) Validation of Analytical Procedures

Q27. Which problem does using a split injection mode help to mitigate?

• Poor peak symmetry due to active sites
• Overloading the column with concentrated samples
• Increasing sensitivity for trace analytes
• Eliminating need for carrier gas

Correct Answer: Overloading the column with concentrated samples

Q28. Which analyte class is least amenable to direct GC analysis without modification?

• Low molecular weight volatile solvents
• Non‑polar hydrocarbons
• High molecular weight polar drugs and peptides
• Volatile halogenated impurities

Correct Answer: High molecular weight polar drugs and peptides

Q29. When is an internal standard method preferred over external calibration in GC quantification?

• When detector response is perfectly stable and matrix absent
• When injection variability or matrix effects can affect analyte response
• When only qualitative identification is required
• When analytes and standards are identical in concentration only

Correct Answer: When injection variability or matrix effects can affect analyte response

Q30. Which practice enhances method robustness for a GC assay intended for routine QC?

• Ignoring column age and never replacing it
• Specifying acceptable ranges for critical parameters (flow, temperature, split ratio) and system suitability checks
• Using a single standard once and never revalidating
• Performing no system suitability and relying on the first run

Correct Answer: Specifying acceptable ranges for critical parameters (flow, temperature, split ratio) and system suitability checks

G S Sachin

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.

Mail- Sachin@pharmacyfreak.com