Applications of mass spectrometry MCQs With Answer

Introduction: Applications of mass spectrometry MCQs With Answer is a focused quiz collection tailored for M.Pharm students studying Advanced Instrumental Analysis (MPA 201T). This set emphasizes practical and conceptual applications of mass spectrometry in pharmaceutical research and industry, covering hyphenated techniques (LC-MS/MS, GC-MS), ionisation methods (ESI, MALDI), tandem MS fragmentation, accurate mass measurements, quantitative bioanalysis, impurity profiling, ADME studies, metabolomics and proteomics, and mass spectrometric imaging. Each question targets skills required for method development, validation, regulatory compliance and interpretation of spectral data encountered in drug discovery, formulation and quality control. The MCQs include concise answers to reinforce learning and exam readiness.

Q1. Which ionisation technique is most suitable for direct analysis of high-molecular-weight proteins with minimal fragmentation?

• Electron ionisation (EI)
• Atmospheric pressure chemical ionisation (APCI)
• Electrospray ionisation (ESI)
• Fast atom bombardment (FAB)

Correct Answer: Electrospray ionisation (ESI)

Q2. In LC-MS/MS bioanalytical assays for pharmacokinetic studies, what is the primary reason to use a heavy-isotope labelled internal standard?

• Enhances chromatographic resolution
• Acts as a preservative to prevent degradation
• Compensates for matrix effects and variable ionisation efficiency
• Improves mass resolution of the instrument

Correct Answer: Compensates for matrix effects and variable ionisation efficiency

Q3. Which mass analyser provides the highest mass accuracy and is commonly used for elemental composition determination in impurity profiling?

• Quadrupole
• Ion trap
• Time-of-flight (TOF) with high-resolution capability
• Magnetic sector with low resolution

Correct Answer: Time-of-flight (TOF) with high-resolution capability

Q4. Tandem MS (MS/MS) is most useful in structural elucidation because it allows:

• Direct measurement of UV absorption of analytes
• Isolation and fragmentation of selected precursor ions to obtain product ion spectra
• Measurement of bulk sample mass without separation
• Generation of isotopic clusters for quantification

Correct Answer: Isolation and fragmentation of selected precursor ions to obtain product ion spectra

Q5. Which hyphenated technique is most appropriate for volatile, thermally stable drug impurities analysis?

• LC-MS
• GC-MS
• MALDI-MS
• Direct infusion ESI-MS

Correct Answer: GC-MS

Q6. In quantitative LC-MS assays, ion suppression commonly arises from:

• Instrument detector aging
• Co-eluting matrix components reducing ionisation efficiency
• Using too high column temperature
• Excessive mass resolution settings

Correct Answer: Co-eluting matrix components reducing ionisation efficiency

Q7. Which application of mass spectrometry is most directly used for identifying metabolites of a new drug in biological matrices?

• Proteomics
• Metabolite identification using LC-MS/MS with accurate mass and fragmentation
• Solid phase microextraction alone
• UV spectroscopy coupled with HPLC

Correct Answer: Metabolite identification using LC-MS/MS with accurate mass and fragmentation

Q8. Matrix-assisted laser desorption/ionisation (MALDI) is particularly advantageous in pharmaceutical research for:

• Quantitative small-molecule bioanalysis in plasma
• Imaging mass spectrometry of tissue distributions and intact biomolecule analysis
• Gas-phase ion chemistry studies only
• Direct GC coupling for volatile compounds

Correct Answer: Imaging mass spectrometry of tissue distributions and intact biomolecule analysis

Q9. Which fragmentation pattern feature is most informative for locating a labile functional group in MS/MS?

• Base peak intensity alone
• Neutral loss corresponding to the functional group mass
• Total ion chromatogram area
• Retention time only

Correct Answer: Neutral loss corresponding to the functional group mass

Q10. High-resolution accurate mass (HRAM) spectrometry aids impurity profiling by:

• Allowing absolute quantitation without standards
• Providing exact mass to determine elemental composition and formula of unknowns
• Replacing need for separation entirely
• Reducing sample preparation time to zero

Correct Answer: Providing exact mass to determine elemental composition and formula of unknowns

Q11. Which MS-based approach is commonly used for targeted quantification of small-molecule drugs in clinical samples with high sensitivity?

• Single quadrupole MS in full scan mode
• Triple quadrupole MS in multiple reaction monitoring (MRM) mode
• Magnetic sector scanning at low resolution
• Direct infusion MALDI-TOF

Correct Answer: Triple quadrupole MS in multiple reaction monitoring (MRM) mode

Q12. Ion mobility spectrometry coupled to MS (IMS-MS) adds value in pharmaceutical analysis by:

• Eliminating the need for ionisation
• Separating isomers and conformers based on gas-phase mobility before mass analysis
• Providing UV spectra for structural identification
• Increasing chromatographic retention time reproducibility

Correct Answer: Separating isomers and conformers based on gas-phase mobility before mass analysis

Q13. In stability-indicating methods for pharmaceuticals, mass spectrometry helps primarily by:

• Increasing tablet hardness
• Detecting and structurally characterising degradation products at trace levels
• Replacing dissolution testing
• Measuring bulk density of powder blends

Correct Answer: Detecting and structurally characterising degradation products at trace levels

Q14. Which factor is critical when developing an LC-MS method to minimize carryover and ensure accurate quantitation?

• Using the narrowest possible column only
• Selecting appropriate wash solvents and injection needle/rinsing protocols
• Always running samples at the highest flow rate
• Switching off the ESI source between injections

Correct Answer: Selecting appropriate wash solvents and injection needle/rinsing protocols

Q15. Proteomics applications of MS in pharmaceutical research primarily use which strategy to identify and quantify proteins?

• Intact protein UV spectroscopy
• Tryptic digestion followed by LC-MS/MS peptide mapping (bottom-up proteomics)
• Direct GC-MS analysis of proteins
• HPLC with refractive index detection

Correct Answer: Tryptic digestion followed by LC-MS/MS peptide mapping (bottom-up proteomics)

Q16. Which statement about accurate mass measurement and isotopic pattern matching is correct for formula confirmation?

• Isotopic pattern matching is irrelevant when accurate mass is known
• Accurate mass combined with isotopic pattern improves confidence in proposed elemental composition
• Only nominal mass is needed for unequivocal formula assignment
• Isotopic patterns are only useful for proteins, not small molecules

Correct Answer: Accurate mass combined with isotopic pattern improves confidence in proposed elemental composition

Q17. In LC-MS method validation for regulatory submission, which parameter specifically addresses the ability to measure an analyte in presence of related substances?

• Linearity
• Specificity/selectivity
• Precision
• Freeze-thaw stability

Correct Answer: Specificity/selectivity

Q18. When using electrospray ionisation for small molecules, increasing mobile phase organic content typically results in:

• Decreased desolvation and reduced signal
• Improved desolvation and often increased ionisation efficiency
• Complete suppression of all ions
• No effect on ionisation efficiency

Correct Answer: Improved desolvation and often increased ionisation efficiency

Q19. Mass spectrometric imaging (MSI) in drug distribution studies provides which advantage over autoradiography?

• Requires radiolabelled drug for detection
• Can provide molecular specificity for parent drug and metabolites without radiolabelling
• Has poorer spatial resolution in all cases
• Only measures total radioactivity

Correct Answer: Can provide molecular specificity for parent drug and metabolites without radiolabelling

Q20. In drug metabolism studies, collision-induced dissociation (CID) in MS/MS is most valuable because it:

• Prevents fragmentation to simplify spectra
• Generates characteristic product ions that reveal substructures and sites of metabolism
• Measures absolute protein concentration directly
• Increases chromatographic retention of metabolites

Correct Answer: Generates characteristic product ions that reveal substructures and sites of metabolism

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