Applications of mass spectrometry MCQs With Answer

Applications of mass spectrometry MCQs With Answer

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Applications of mass spectrometry MCQs With Answer offers M.Pharm students a focused way to master how MS technologies drive modern pharmaceutical analysis. From quantitative bioanalysis and metabolite identification to impurity profiling, proteomics, and elemental impurity testing, mass spectrometry underpins key decisions across discovery, development, and quality control. These MCQs emphasize practical applications—choosing the right ionization source, detector, or acquisition mode; tackling matrix effects; designing validation strategies; and interpreting advanced methods such as HRMS, imaging MS, HDX-MS, IM-MS, and ICP-MS. Work through the questions to sharpen exam readiness and deepen real-world problem-solving skills relevant to pharmacokinetics, biotherapeutics characterization, genotoxic impurities, tissue distribution, and regulatory-compliant bioanalysis.

Q1. For high-sensitivity quantitative bioanalysis of small-molecule drugs in plasma for pharmacokinetics, the most appropriate platform is:

  • HPLC with UV detection
  • GC with flame ionization detection (GC-FID)
  • LC–MS/MS on a triple quadrupole using MRM transitions
  • NMR spectroscopy

Correct Answer: LC–MS/MS on a triple quadrupole using MRM transitions

Q2. Which technique is most suitable for quantifying elemental impurities in drug products as per ICH Q3D?

  • MALDI-TOF MS
  • ICP–MS
  • ESI–MS
  • FT-IR spectroscopy

Correct Answer: ICP–MS

Q3. To visualize spatial distribution of a drug and its metabolites directly in tissue sections without labels, you would use:

  • HPLC-UV
  • Scanning electron microscopy
  • MALDI imaging mass spectrometry (MALDI-MSI)
  • PET imaging

Correct Answer: MALDI imaging mass spectrometry (MALDI-MSI)

Q4. The best approach for comprehensive identification of Phase I and Phase II metabolites in discovery DMPK is:

  • GC-FID after derivatization
  • NMR of pooled fractions only
  • LC–HRMS (QTOF/Orbitrap) with accurate-mass MS/MS
  • HPLC with diode-array detection

Correct Answer: LC–HRMS (QTOF/Orbitrap) with accurate-mass MS/MS

Q5. In quantitative LC–MS/MS bioanalysis, the most effective strategy to correct for ion suppression/enhancement is:

  • Using external calibration with neat solutions
  • Adding a stable isotope–labeled internal standard that co-elutes with the analyte
  • Increasing source temperature only
  • Shortening the chromatographic run

Correct Answer: Adding a stable isotope–labeled internal standard that co-elutes with the analyte

Q6. To distinguish isobaric compounds that share the same nominal mass during metabolite identification, the preferred MS strategy is:

  • High-resolution accurate-mass MS with tandem MS (HRMS/MS)
  • Size-exclusion chromatography
  • Fluorescence spectroscopy
  • Thin-layer chromatography

Correct Answer: High-resolution accurate-mass MS with tandem MS (HRMS/MS)

Q7. For characterization of biotherapeutics via peptide mapping to confirm sequence and PTMs, the application most commonly used is:

  • SDS-PAGE densitometry
  • ELISA
  • Bottom-up LC–MS/MS peptide mapping
  • Powder X-ray diffraction

Correct Answer: Bottom-up LC–MS/MS peptide mapping

Q8. Assessing higher-order structure and conformational dynamics of proteins in formulation studies is best achieved by:

  • Hydrogen–deuterium exchange mass spectrometry (HDX–MS)
  • Circular dichroism (CD) spectroscopy only
  • Size-exclusion chromatography with UV detection
  • Thermogravimetric analysis

Correct Answer: Hydrogen–deuterium exchange mass spectrometry (HDX–MS)

Q9. You need to elucidate the structure of an unknown trace impurity (ppm level) in a drug substance. The most informative analytical choice is:

  • UV–Vis spectroscopy
  • LC–HRMS with MS/MS (and potentially MSn)
  • Refractive index detection
  • Polarimetry

Correct Answer: LC–HRMS with MS/MS (and potentially MSn)

Q10. For trace-level quantification of nitrosamine impurities in drug products, a widely adopted analytical approach is:

  • HPLC-UV with gradient elution
  • GC-FID with headspace sampling
  • LC–MS/MS in MRM mode using isotopically labeled internal standards
  • Thin-layer chromatography with densitometry

Correct Answer: LC–MS/MS in MRM mode using isotopically labeled internal standards

Q11. Targeted quantification of a therapeutic protein via its signature peptides in plasma is most effectively performed using:

  • Triple quadrupole LC–MS/MS in SRM/MRM mode
  • Gel electrophoresis with silver staining
  • MALDI-TOF intact mass profiling only
  • UV at 280 nm

Correct Answer: Triple quadrupole LC–MS/MS in SRM/MRM mode

Q12. Determining enantiomeric purity of a chiral drug during release testing by MS-based methods is best achieved using:

  • Normal-phase LC–MS without a chiral selector
  • Chiral LC–MS/MS with a chiral stationary phase
  • MALDI imaging
  • ICP–MS

Correct Answer: Chiral LC–MS/MS with a chiral stationary phase

Q13. Ultra-trace quantification of 14C-labeled drug in microdosing human ADME studies typically uses:

  • Accelerator mass spectrometry (AMS)
  • Neutron activation analysis
  • ICP–OES
  • Surface plasmon resonance

Correct Answer: Accelerator mass spectrometry (AMS)

Q14. Rapid profiling of N-glycan distributions from a monoclonal antibody for comparability is commonly performed by:

  • MALDI-TOF MS of released glycans
  • GC-MS of underivatized glycans
  • UV-Vis spectroscopy at 214 nm
  • Capillary electrophoresis without MS

Correct Answer: MALDI-TOF MS of released glycans

Q15. When a pharmacokinetic study requires quantitation across four to five orders of magnitude with high selectivity, the preferred MS configuration is:

  • Single quadrupole LC–MS
  • Triple quadrupole LC–MS/MS operating in MRM
  • Ion trap MS with full-scan acquisition
  • MALDI-TOF in linear mode

Correct Answer: Triple quadrupole LC–MS/MS operating in MRM

Q16. In bioanalytical method validation for LC–MS/MS, which experiment directly evaluates ion suppression or enhancement from matrix components?

  • Recovery experiment (extraction efficiency)
  • Matrix effect assessment by post-extraction addition
  • Carryover check
  • Freeze–thaw stability

Correct Answer: Matrix effect assessment by post-extraction addition

Q17. To map spatial distribution of metals (e.g., Pt from a chemotherapeutic) in tissue sections, you would choose:

  • MALDI-MSI
  • LA–ICP–MS (laser ablation ICP–MS)
  • SIMS with organic ion detection only
  • Atomic force microscopy

Correct Answer: LA–ICP–MS (laser ablation ICP–MS)

Q18. Analysis of volatile or semi-volatile genotoxic impurities and residual solvents is best performed using:

  • GC–MS (often with headspace or SPME sampling)
  • HPLC with refractive index detection
  • Capillary electrophoresis with UV
  • MALDI-TOF MS

Correct Answer: GC–MS (often with headspace or SPME sampling)

Q19. Which application is most appropriately addressed by top-down MS in biopharmaceutical analysis?

  • Quantifying small molecules at ng/mL levels
  • Intact proteoform characterization including labile PTMs
  • Measuring osmolality of formulations
  • Determining logP of new chemical entities

Correct Answer: Intact proteoform characterization including labile PTMs

Q20. Adding ion mobility to MS in drug metabolism studies primarily provides which extra descriptor that aids isomer/isobar differentiation?

  • Extinction coefficient
  • Collision cross section (CCS) values
  • pKa
  • Boiling point

Correct Answer: Collision cross section (CCS) values

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