GC-MS/MS: instrumentation and applications MCQs With Answer

Gas chromatography–tandem mass spectrometry (GC-MS/MS) is a powerful analytical platform used to separate, identify, and quantify volatile and semi-volatile compounds with high sensitivity and selectivity. This concise overview emphasizes GC-MS/MS instrumentation — injectors, capillary columns, transfer lines, ionization sources (EI and CI), collision cells, and triple‑quadrupole analyzers — and practical applications in pharmaceutical analysis, drug metabolism, forensic toxicology, environmental monitoring, stability testing, and residue analysis. Core principles such as scan modes (full-scan, SIM, MRM), collision-induced dissociation, limits of detection, matrix effects, and quantitative workflows are highlighted to prepare B.Pharm students for laboratory practice and exam-style MCQs. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which component in GC-MS/MS maintains the temperature required for chromatographic separation?

• Injector
• Mass analyzer
• Column oven
• Ion source

Correct Answer: Column oven

Q2. What is the main advantage of tandem mass spectrometry (MS/MS) over single-stage MS in quantitative assays?

• Lower running cost
• Improved chromatographic resolution
• Higher selectivity and reduced background
• Faster column equilibration

Correct Answer: Higher selectivity and reduced background

Q3. Which ionization method is most commonly used in GC-MS/MS for small volatile molecules?

• Electrospray ionization (ESI)
• MALDI
• Electron ionization (EI)
• Atmospheric pressure chemical ionization (APCI)

Correct Answer: Electron ionization (EI)

Q4. In triple-quadrupole MS, which quadrupole serves as the collision cell?

• Q1
• Q2
• Q3
• All three simultaneously

Correct Answer: Q2

Q5. What is MRM (multiple reaction monitoring) primarily used for?

• Full-scan qualitative profiling
• Targeted quantitative analysis with high specificity
• Column temperature programming
• Ion source tuning

Correct Answer: Targeted quantitative analysis with high specificity

Q6. Which parameter controls the energy applied for fragmentation in the collision cell?

• Dwell time
• Collision energy
• Transfer line temperature
• Carrier gas flow

Correct Answer: Collision energy

Q7. Which GC inlet type allows for large-volume injections and splitless introduction for trace analysis?

• Split inlet
• On-column inlet
• Programmed temperature vaporizing (PTV) inlet
• Headspace sampler

Correct Answer: Programmed temperature vaporizing (PTV) inlet

Q8. In GC-MS/MS, what is the purpose of a transfer line between the GC and MS?

• To cool the column effluent
• To maintain analyte vaporization and prevent condensation
• To ionize the analytes
• To perform chromatographic separation

Correct Answer: To maintain analyte vaporization and prevent condensation

Q9. Which scan mode is best for discovering unknown compounds in a sample?

• MRM
• SIM (selected ion monitoring)
• Full-scan mass spectrum
• Product ion scan only

Correct Answer: Full-scan mass spectrum

Q10. Chemical ionization (CI) differs from EI primarily because CI:

• Produces more extensive fragmentation than EI
• Is a hard ionization technique
• Produces more prominent molecular ions and less fragmentation
• Requires liquid chromatography

Correct Answer: Produces more prominent molecular ions and less fragmentation

Q11. Which gas is commonly used as the collision gas in Q2 for CID (collision-induced dissociation)?

• Oxygen
• Nitrogen
• Helium
• Argon

Correct Answer: Argon

Q12. In GC-MS/MS quantitation, why are stable isotope-labeled internal standards often used?

• They increase chromatographic retention time
• They provide matrix-matched calibration and correct for losses
• They change ionization method from EI to CI
• They eliminate the need for calibration curves

Correct Answer: They provide matrix-matched calibration and correct for losses

Q13. What does SRM (selected reaction monitoring) refer to in tandem MS?

• Monitoring a precursor ion only
• Monitoring a specific precursor-to-product ion transition
• Monitoring all product ions simultaneously
• Scanning full mass range repeatedly

Correct Answer: Monitoring a specific precursor-to-product ion transition

Q14. Which factor most directly affects chromatographic peak width and resolution in GC?

• Mass analyzer type
• Column length and internal diameter
• Ion source design
• Collision energy

Correct Answer: Column length and internal diameter

Q15. What is the primary reason for derivatization prior to GC-MS/MS analysis of certain pharmaceuticals?

• To reduce analyte volatility
• To increase analyte polarity
• To improve volatility and thermal stability for GC separation
• To decrease molecular weight

Correct Answer: To improve volatility and thermal stability for GC separation

Q16. In method validation for GC-MS/MS quantitative assays, which metric assesses the smallest concentration that can be measured with acceptable precision and accuracy?

• Linearity range
• Limit of detection (LOD)
• Limit of quantitation (LOQ)
• Retention index

Correct Answer: Limit of quantitation (LOQ)

Q17. Which maintenance task helps prevent contamination of the ion source in GC-MS/MS?

• Replacing the chromatographic column monthly
• Regularly cleaning or replacing the ion source and liners
• Changing carrier gas frequently
• Reducing oven temperature permanently

Correct Answer: Regularly cleaning or replacing the ion source and liners

Q18. In a triple quadrupole operating in MRM, what is ‘dwell time’?

• The time for column temperature ramp
• The time spent monitoring a single transition per cycle
• The total run time of the analysis
• The time for ionization to occur

Correct Answer: The time spent monitoring a single transition per cycle

Q19. Which application is GC-MS/MS especially suited for in pharmaceutical analysis?

• High-molecular-weight protein sequencing
• Analysis of non-volatile large peptides
• Quantification of volatile drug impurities and metabolites
• Direct analysis of intact antibodies

Correct Answer: Quantification of volatile drug impurities and metabolites

Q20. What does ‘selectivity’ mean in the context of GC-MS/MS assays?

• Ability to separate analytes by boiling point only
• Capacity to detect only the most abundant ions
• Ability to distinguish analyte signal from other matrix signals
• Speed of chromatographic run

Correct Answer: Ability to distinguish analyte signal from other matrix signals

Q21. Which mass analyzer type commonly provides high resolution and accurate mass but is less common for routine GC-MS/MS triple-quad workflows?

• Quadrupole
• Ion trap
• Time-of-flight (TOF) or Orbitrap
• Photomultiplier tube

Correct Answer: Time-of-flight (TOF) or Orbitrap

Q22. Matrix effects in GC-MS/MS are typically caused by:

• Column length variations
• Interference from co-eluting matrix components altering ionization
• Incorrect oven temperature only
• Using helium as carrier gas

Correct Answer: Interference from co-eluting matrix components altering ionization

Q23. For pesticide residue analysis in food by GC-MS/MS, which sample preparation is often required?

• Protein sequencing
• Liquid-liquid extraction or QuEChERS with cleanup
• Direct injection without cleanup
• Gel electrophoresis

Correct Answer: Liquid-liquid extraction or QuEChERS with cleanup

Q24. What role does the electron multiplier detector play in many GC-MS systems?

• Separating ions by m/z
• Generating ions from neutral molecules
• Amplifying ion signal for detection
• Controlling carrier gas flow

Correct Answer: Amplifying ion signal for detection

Q25. In interpreting MS/MS spectra, product ions are used to:

• Adjust column oven settings
• Confirm structural fragments of the precursor and provide selectivity
• Calibrate the carrier gas purity
• Measure column bleed only

Correct Answer: Confirm structural fragments of the precursor and provide selectivity

Q26. Which parameter would you adjust to increase sensitivity for a low-abundance MRM transition?

• Decrease collision gas pressure to zero
• Increase dwell time for that transition
• Shorten column length to 5 mm
• Switch from EI to MALDI

Correct Answer: Increase dwell time for that transition

Q27. Why is helium commonly used as a carrier gas in GC-MS, despite cost considerations?

• It reacts with analytes to form adducts
• It provides optimal efficiency and chromatographic performance on capillary columns
• It is heavier than nitrogen and increases retention
• It ionizes molecules in the source

Correct Answer: It provides optimal efficiency and chromatographic performance on capillary columns

Q28. Which practice improves assay robustness for routine GC-MS/MS in a pharmaceutical QC lab?

• Ignoring system suitability checks
• Using consistent internal standards and regular calibration checks
• Changing method parameters each run to optimize
• Avoiding maintenance to save time

Correct Answer: Using consistent internal standards and regular calibration checks

Q29. What is the effect of increasing column temperature ramp rate in GC?

• Longer analysis times and broader peaks
• Faster elution with potential loss of separation for closely eluting analytes
• No change in retention times
• Improves ionization efficiency in the MS

Correct Answer: Faster elution with potential loss of separation for closely eluting analytes

Q30. In forensic toxicology, GC-MS/MS is preferred for certain drug analyses because it offers:

• Low specificity but high throughput
• High sensitivity, selectivity, and confirmatory fragmentation patterns
• Only qualitative results without quantitation
• Inability to analyze volatile compounds

Correct Answer: High sensitivity, selectivity, and confirmatory fragmentation patterns

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