Calibration of Gas Chromatograph (GC) MCQs With Answer

Calibration of Gas Chromatograph (GC) is a critical skill for B. Pharm students involved in pharmaceutical analysis. This introduction covers key concepts like GC calibration, calibration curve, response factor, internal and external standards, linearity, LOD, LOQ, and system suitability. Proper calibration ensures accurate, precise, and traceable quantitative results by relating detector response to known concentrations, addressing matrix effects, and controlling instrument drift. Understanding standard preparation, verification frequency, and common pitfalls (e.g., detector saturation, carryover) is essential for reliable assay performance in pharmacopeial and regulatory contexts. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary purpose of calibrating a gas chromatograph for quantitative analysis?

• To clean the GC column before analysis
• To relate detector response to known concentrations for accurate quantitation
• To reduce carrier gas consumption
• To adjust injector temperature only

Correct Answer: To relate detector response to known concentrations for accurate quantitation

Q2. Which statement best describes an internal standard in GC calibration?

• A compound added only to the calibration standards
• A compound that is naturally present in all samples
• A compound added in a constant amount to all samples and standards to correct for variability
• A solvent used to dilute standards

Correct Answer: A compound added in a constant amount to all samples and standards to correct for variability

Q3. How is the relative response factor (RRF) defined?

• The ratio of retention times between analyte and standard
• The ratio of detector response per unit concentration of analyte to that of the standard
• The difference in peak heights of two analytes
• The ratio of solvent peak area to analyte area

Correct Answer: The ratio of detector response per unit concentration of analyte to that of the standard

Q4. On a calibration plot for GC quantitation, which axis typically represents concentration?

• Y-axis (detector response)
• X-axis (concentration)
• Z-axis (temperature)
• Legend area

Correct Answer: X-axis (concentration)

Q5. Limit of detection (LOD) in GC calibration is best described as:

• The concentration where the calibration curve becomes non-linear
• The lowest concentration that can be distinguished from background noise
• The concentration with 100% recovery
• The highest measurable concentration without dilution

Correct Answer: The lowest concentration that can be distinguished from background noise

Q6. What is the practical definition of limit of quantitation (LOQ) in GC method calibration?

• The lowest concentration that can be measured with acceptable precision and accuracy
• The concentration at which peaks overlap
• The highest calibrant used in the curve
• The detector’s maximum linear response

Correct Answer: The lowest concentration that can be measured with acceptable precision and accuracy

Q7. Which statistical parameter is commonly used to evaluate linearity of a GC calibration curve?

• Retention index
• Resolution
• Correlation coefficient (r or r²) from linear regression
• Carrier gas pressure

Correct Answer: Correlation coefficient (r or r²) from linear regression

Q8. Which of the following is NOT a typical system suitability criterion for GC quantitative analysis?

• Theoretical plates (efficiency)
• Resolution between critical peaks
• Repeatability of retention time and peak area (RSD%)
• Mass spectrometer ion source voltage

Correct Answer: Mass spectrometer ion source voltage

Q9. Which preparation approach is considered most accurate for making calibration standards?

• Volumetric dilution by eye
• Gravimetric preparation using accurate weighing and dilution
• Using pipette tips without calibration
• Preparing standards directly in the injector

Correct Answer: Gravimetric preparation using accurate weighing and dilution

Q10. When is it appropriate to use relative response factor (RRF) instead of absolute response factor?

• When no internal standard is used
• When an internal standard method is applied to correct for variability
• Only for qualitative analysis
• Only when using TCD detector

Correct Answer: When an internal standard method is applied to correct for variability

Q11. How does using a high split ratio during injection affect GC calibration?

• Increases sensitivity and lowers LOD
• Reduces the amount of analyte entering the column, which can decrease sensitivity
• Has no effect on detector response
• Makes peaks wider and increases retention times drastically

Correct Answer: Reduces the amount of analyte entering the column, which can decrease sensitivity

Q12. Detector saturation in GC calibration typically leads to what effect on the calibration curve?

• Improved linearity at high concentrations
• Deviation from linearity at high concentrations due to plateauing response
• Shorter retention times
• A change in carrier gas composition

Correct Answer: Deviation from linearity at high concentrations due to plateauing response

Q13. Why is matrix-matched calibration recommended in some pharmaceutical GC assays?

• To increase column lifetime
• To correct for matrix effects that alter detector response or extraction efficiency
• To reduce the number of calibration points
• To speed up run times

Correct Answer: To correct for matrix effects that alter detector response or extraction efficiency

Q14. Best practice for storing calibration standards is to:

• Leave them open at room temperature
• Store in amber glass vials, tightly capped, under recommended temperature conditions
• Keep them in plastic bags exposed to light
• Freeze and thaw repeatedly before use

Correct Answer: Store in amber glass vials, tightly capped, under recommended temperature conditions

Q15. When should calibration verification be performed on a GC used for routine pharmaceutical assays?

• Only once during instrument installation
• Regularly, after major maintenance, and before critical sample batches
• Never, if the instrument looks clean
• Only when changing carrier gas

Correct Answer: Regularly, after major maintenance, and before critical sample batches

Q16. Which property is most important when choosing an internal standard for GC calibration?

• It must co-elute exactly with the analyte
• It must be chemically similar in behavior but not present in the sample and must not co-elute
• It should have the highest detector response
• It must be the cheapest available compound

Correct Answer: It must be chemically similar in behavior but not present in the sample and must not co-elute

Q17. For qualitative identification using GC, calibration primarily ensures:

• That peak areas are maximal
• Retention times are comparable to reference standards and retention time locking is maintained
• That all analytes are volatile
• That detector noise is eliminated

Correct Answer: Retention times are comparable to reference standards and retention time locking is maintained

Q18. Why apply weighted regression (e.g., 1/x) to a GC calibration curve?

• To ignore low-concentration points
• To compensate for heteroscedasticity where variance increases with concentration
• To force the intercept to zero
• To reduce analysis time

Correct Answer: To compensate for heteroscedasticity where variance increases with concentration

Q19. Which measurement is generally preferred for GC quantitative analysis and why?

• Peak height, because it is less affected by baseline noise
• Peak area, because it accounts for peak shape and provides better accuracy and precision for broad or asymmetric peaks
• Retention time, because it indicates concentration
• Column temperature, because it correlates with analyte mass

Correct Answer: Peak area, because it accounts for peak shape and provides better accuracy and precision for broad or asymmetric peaks

Q20. Why are multiple calibration levels (e.g., five or more) preferred in GC calibration?

• To waste more standards
• To define the analytical range, assess linearity, and detect non-linearity across concentrations
• To increase run time unnecessarily
• To avoid using internal standards

Correct Answer: To define the analytical range, assess linearity, and detect non-linearity across concentrations

Q21. What is calibration drift in GC systems?

• A sudden, permanent change in instrument firmware
• A gradual change in instrument response or retention time over time, affecting accuracy
• The expected variation in peak area between injections
• A method to improve calibration stability

Correct Answer: A gradual change in instrument response or retention time over time, affecting accuracy

Q22. Which regulatory guideline is commonly referred to for validation of chromatographic methods including calibration?

• ICH Q2(R1)
• ISO 9001
• GMP Annex 1
• PAS 99

Correct Answer: ICH Q2(R1)

Q23. Which practice helps prevent sample carryover that could affect calibration and quantitation?

• Increasing oven temperature between runs only
• Implementing adequate injector needle wash and running blank injections
• Using the same vial for all injections
• Reducing carrier gas flow to zero

Correct Answer: Implementing adequate injector needle wash and running blank injections

Q24. What is the purpose of bracketing calibration in a long analytical run?

• To double the number of calibration standards used
• To run calibration standards before and after a batch of samples to monitor and correct for drift
• To change columns automatically
• To increase detector sensitivity mid-run

Correct Answer: To run calibration standards before and after a batch of samples to monitor and correct for drift

Q25. Which GC detector is considered most “universal” for permanent gases and inorganic components?

• Flame Ionization Detector (FID)
• Mass Spectrometer (MS)
• Thermal Conductivity Detector (TCD)
• Electron Capture Detector (ECD)

Correct Answer: Thermal Conductivity Detector (TCD)

Q26. Which formula correctly represents the Relative Response Factor (RRF) using areas and concentrations?

• RRF = (Area_std / Conc_std) / (Area_analyte / Conc_analyte)
• RRF = (Area_analyte / Conc_analyte) / (Area_std / Conc_std)
• RRF = Area_analyte × Area_std
• RRF = Conc_analyte – Conc_std

Correct Answer: RRF = (Area_analyte / Conc_analyte) / (Area_std / Conc_std)

Q27. For regulatory pharmaceutical assays, an acceptable coefficient of determination (r²) for a calibration curve is commonly:

• Less than 0.900
• Between 0.950 and 0.970
• Typically greater than 0.995, depending on method requirements
• Exactly zero

Correct Answer: Typically greater than 0.995, depending on method requirements

Q28. What is the main purpose of running a solvent blank during a calibration sequence?

• To increase sample throughput
• To check for contamination, carryover, or background peaks that could bias calibration
• To recalibrate the injection port temperature
• To flush the carrier gas line only

Correct Answer: To check for contamination, carryover, or background peaks that could bias calibration

Q29. When is the standard addition method preferred over external calibration in GC quantitation?

• When analyte concentrations are extremely high only
• When matrix effects significantly suppress or enhance analyte response and need compensation
• When no internal standard is available and matrix is simple
• When calibration curves are always linear

Correct Answer: When matrix effects significantly suppress or enhance analyte response and need compensation

Q30. How can column bleed affect calibration quality in GC analysis?

• It reduces carrier gas purity only
• It increases baseline noise and can reduce sensitivity and accuracy of low-level calibration points
• It improves peak shape for late-eluting analytes
• It shortens analysis time

Correct Answer: It increases baseline noise and can reduce sensitivity and accuracy of low-level calibration points

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