Principles of Mass Spectrometry MCQs With Answer

Principles of Mass Spectrometry MCQs With Answer

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Principles of Mass Spectrometry MCQs With Answer

Mass spectrometry is a core analytical technique for B. Pharm students, combining ionization, mass analyzers, detectors, and data interpretation to identify and quantify drugs, metabolites, and impurities. This set of MCQs covers fundamental principles—ionization methods (ESI, MALDI, EI, CI), mass-to-charge ratio (m/z), mass analyzers (quadrupole, TOF, Orbitrap, FT-ICR), fragmentation patterns, isotopic distribution, resolution and mass accuracy, tandem MS (MS/MS) and quantitative approaches like SRM/MRM. Emphasis is on practical pharmaceutical applications, sample preparation, adduct formation, and troubleshooting ion suppression. Clear explanations after each question will reinforce learning. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What does the mass-to-charge ratio (m/z) represent in mass spectrometry?

  • The mass of an ion divided by its charge
  • The molecular weight multiplied by the charge
  • The ratio of sample concentration to detector signal
  • The time an ion spends in the detector

Correct Answer: The mass of an ion divided by its charge

Q2. Which ionization technique is most suitable for analyzing large, non-volatile biomolecules like peptides?

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

Correct Answer: Electrospray ionization (ESI)

Q3. In electron ionization (EI), what is a common characteristic of the resulting mass spectrum?

  • Predominant intact molecular ion with few fragments
  • Extensive fragmentation and reproducible patterns
  • No ionization of organic molecules
  • Only singly charged adducts are observed

Correct Answer: Extensive fragmentation and reproducible patterns

Q4. Which mass analyzer separates ions based on their flight time and is well suited for high-speed analysis?

  • Quadrupole
  • Time-of-Flight (TOF)
  • Ion trap
  • Orbitrap

Correct Answer: Time-of-Flight (TOF)

Q5. What is the primary advantage of high-resolution mass spectrometry (HRMS) in pharmaceutical analysis?

  • Lower instrument cost
  • Ability to distinguish ions with very close m/z values for elemental composition
  • Faster sample throughput than low-resolution instruments
  • Elimination of the need for chromatography

Correct Answer: Ability to distinguish ions with very close m/z values for elemental composition

Q6. Which term describes the ion corresponding to the intact molecule without fragmentation?

  • Base peak
  • Fragment ion
  • Molecular ion (M+• or [M]+)
  • Isotopologue

Correct Answer: Molecular ion (M+• or [M]+)

Q7. In tandem mass spectrometry (MS/MS), what is the primary purpose of collision-induced dissociation (CID)?

  • To increase ion acceleration into the detector
  • To fragment selected precursor ions for structural information
  • To generate more molecular ions without fragmentation
  • To separate ions by mobility in gas phase

Correct Answer: To fragment selected precursor ions for structural information

Q8. Which detector type is commonly used for high-sensitivity detection of ions in LC-MS systems?

  • Faraday cup
  • Electron multiplier (dynode)
  • Photomultiplier tube
  • Thermal conductivity detector

Correct Answer: Electron multiplier (dynode)

Q9. What does resolution in mass spectrometry refer to?

  • The speed at which data are acquired
  • The ability to separate two adjacent m/z signals
  • The maximum m/z measurable by the instrument
  • The brightness of the detector signal

Correct Answer: The ability to separate two adjacent m/z signals

Q10. Which adduct is commonly observed in electrospray ionization of small molecules in positive mode?

  • [M−H]−
  • [M+H]+
  • [M+Cl]−
  • [M+O2]+

Correct Answer: [M+H]+

Q11. What is the ‘base peak’ in a mass spectrum?

  • The ion with the highest m/z value
  • The most abundant ion peak, set as 100% intensity
  • The first ion detected by the instrument
  • The ion corresponding to the molecular ion

Correct Answer: The most abundant ion peak, set as 100% intensity

Q12. In quantitative LC-MS/MS, which mode monitors predefined precursor and product ion transitions for high specificity?

  • Full scan
  • Selected ion monitoring (SIM)
  • Selected reaction monitoring / Multiple reaction monitoring (SRM/MRM)
  • Neutral loss scan

Correct Answer: Selected reaction monitoring / Multiple reaction monitoring (SRM/MRM)

Q13. Which phenomenon can cause decreased ionization efficiency in LC-MS, especially with complex matrices?

  • Isotopic enrichment
  • Ion suppression
  • Increased resolution
  • Mass calibration drift

Correct Answer: Ion suppression

Q14. Which isotopic pattern indicates the presence of chlorine in a compound?

  • One major peak only
  • A +2 m/z peak at ~32% relative intensity
  • A +1 m/z peak at ~50% relative intensity
  • A triplet pattern from 0 to +3 m/z

Correct Answer: A +2 m/z peak at ~32% relative intensity

Q15. What is the most useful mass spectral feature to propose a molecular formula using high-resolution data?

  • Retention time in LC
  • Exact mass (accurate mass) of the ion in daltons with ppm error
  • Base peak intensity alone
  • Number of isotopic peaks only

Correct Answer: Exact mass (accurate mass) of the ion in daltons with ppm error

Q16. Which quadrupole function allows only ions of a selected m/z to pass to the detector?

  • Full-scan mode
  • Product ion scan
  • Selected ion monitoring (SIM)
  • All-ion fragmentation

Correct Answer: Selected ion monitoring (SIM)

Q17. In MALDI mass spectrometry, what role does the matrix play?

  • Acts as the detector for ions
  • Absorbs laser energy and assists desorption/ionization of analyte
  • Separates ions by mass
  • Provides a solvent for LC separation

Correct Answer: Absorbs laser energy and assists desorption/ionization of analyte

Q18. How is mass accuracy commonly reported in high-resolution MS?

  • As percentage relative intensity
  • In parts per million (ppm)
  • As m/z units only
  • In volts

Correct Answer: In parts per million (ppm)

Q19. Which instrument provides the highest resolving power among common mass analyzers?

  • Quadrupole
  • TOF
  • Orbitrap or FT-ICR depending on configuration
  • Ion mobility spectrometer

Correct Answer: Orbitrap or FT-ICR depending on configuration

Q20. What is an isotopologue?

  • An ion formed by loss of a neutral fragment
  • A molecule differing only in isotopic composition (e.g., 13C vs 12C)
  • A charged adduct with sodium
  • A calibration standard

Correct Answer: A molecule differing only in isotopic composition (e.g., 13C vs 12C)

Q21. Why are internal standards used in quantitative MS assays?

  • To improve chromatographic separation
  • To compensate for variability in sample preparation and ionization
  • To increase ionization suppression
  • To change mass resolution

Correct Answer: To compensate for variability in sample preparation and ionization

Q22. Which fragmentation rule helps predict cleavage in mass spectrometry for peptides?

  • McLafferty rearrangement only
  • Charge-directed cleavage at peptide bonds producing b and y ions
  • Only neutral losses of water occur
  • No predictable fragmentation occurs for peptides

Correct Answer: Charge-directed cleavage at peptide bonds producing b and y ions

Q23. In electrospray ionization, why are multiply charged ions advantageous for large molecules?

  • They reduce chromatographic retention time
  • They bring high mass molecules into a lower m/z range accessible to analysers
  • They always produce simpler spectra
  • They prevent fragmentation completely

Correct Answer: They bring high mass molecules into a lower m/z range accessible to analysers

Q24. What is the common neutral loss observed for phosphopeptides under MS/MS?

  • Loss of CO2 (44 Da)
  • Loss of H2O (18 Da)
  • Loss of H3PO4 (98 Da)
  • Loss of NH3 (17 Da)

Correct Answer: Loss of H3PO4 (98 Da)

Q25. Which calibration method is essential to maintain mass accuracy over time?

  • External calibration only before each sample
  • Internal or lock-mass calibration during acquisition
  • No calibration is needed for high-resolution instruments
  • Using UV absorbance standards

Correct Answer: Internal or lock-mass calibration during acquisition

Q26. What does ‘monoisotopic mass’ refer to?

  • The average mass of all isotopes combined
  • The mass of the molecule containing the most abundant isotope of each element (e.g., all 12C)
  • The mass of the heaviest isotopologue
  • The mass measured at low resolution only

Correct Answer: The mass of the molecule containing the most abundant isotope of each element (e.g., all 12C)

Q27. Which scanning mode is useful for discovering unknown compounds in a sample?

  • Full-scan high-resolution MS
  • Selected reaction monitoring (SRM)
  • Neutral loss focusing only
  • SIM of one m/z only

Correct Answer: Full-scan high-resolution MS

Q28. What common artifact can appear when sodium is present in electrospray samples?

  • Formation of [M+Na]+ adduct peaks
  • Complete suppression of all ions
  • Always generating only negative ions
  • Loss of resolution in the detector

Correct Answer: Formation of [M+Na]+ adduct peaks

Q29. In triple quadrupole MS used for quantitation, what is Q2 typically used for?

  • Mass filtering of precursor ions only
  • Collision cell for fragmentation (CID)
  • Final mass filtering before the detector
  • Ion source ionization

Correct Answer: Collision cell for fragmentation (CID)

Q30. Which practice improves selectivity and sensitivity in LC-MS assays for trace-level drug quantitation?

  • Using guard-free columns without cleanup
  • Optimized sample cleanup, appropriate internal standard, and targeted MRM transitions
  • Relying solely on full-scan MS without chromatography
  • Increasing detector voltage without method validation

Correct Answer: Optimized sample cleanup, appropriate internal standard, and targeted MRM transitions

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