Mass spectrometry principle MCQs With Answer

Mass spectrometry principle MCQs With Answer

This collection of MCQs is designed for M.Pharm students studying Advanced Instrumental Analysis (MPA 201T). The questions focus on fundamental and advanced principles of mass spectrometry relevant to pharmaceutical analysis, including ionization methods, mass analyzers, detectors, fragmentation, accuracy, resolution, and tandem MS strategies used for structure elucidation and quantification. Each item tests conceptual understanding and practical implications such as matrix effects, adduct formation, and selection of methods for metabolite identification or trace-level drug quantitation. Use these questions for self-assessment, exam preparation, and to deepen your grasp of MS techniques applied in drug development and regulatory environments.

Q1. Which parameter does mass spectrometry directly measure?

• Absolute mass in grams
• Mass-to-charge ratio (m/z)
• Ionization energy in electronvolts
• Retention time in minutes

Correct Answer: Mass-to-charge ratio (m/z)

Q2. Which ionization technique is best suited for analyzing large, non-volatile biomolecules like proteins with minimal fragmentation?

• Electron ionization (EI)
• Electrospray ionization (ESI)
• Chemical ionization (CI)
• Atomic absorption

Correct Answer: Electrospray ionization (ESI)

Q3. Which mass analyzer separates ions based on differences in time-of-flight after acceleration to the same kinetic energy?

• Quadrupole
• Ion trap
• Time-of-flight (TOF)
• Magnetic sector

Correct Answer: Time-of-flight (TOF)

Q4. In tandem mass spectrometry (MS/MS), what is the primary role of collision-induced dissociation (CID)?

• To ionize neutral molecules
• To separate ions by m/z
• To fragment selected precursor ions for structural information
• To detect ions with higher sensitivity

Correct Answer: To fragment selected precursor ions for structural information

Q5. Which detector is commonly used in modern MS for single-ion counting and high sensitivity?

• Faraday cup
• Electron multiplier (photomultiplier)
• Thermocouple
• Optical CCD

Correct Answer: Electron multiplier (photomultiplier)

Q6. What does resolution in mass spectrometry describe?

• The mass range an instrument can measure
• The ability to distinguish two adjacent m/z peaks
• The ionization efficiency for a compound
• The detector response linearity

Correct Answer: The ability to distinguish two adjacent m/z peaks

Q7. Which ionization method commonly produces radical cations and is widely used for small volatile molecules in GC-MS?

• Electrospray ionization (ESI)
• Electron ionization (EI)
• Matrix-assisted laser desorption/ionization (MALDI)
• Atmospheric pressure chemical ionization (APCI)

Correct Answer: Electron ionization (EI)

Q8. Mass accuracy is often expressed in parts per million (ppm). Which scenario corresponds to a mass error of 5 ppm for a nominal m/z 500 ion?

• An absolute error of 0.005 m/z units
• An absolute error of 0.05 m/z units
• An absolute error of 0.5 m/z units
• An absolute error of 5 m/z units

Correct Answer: An absolute error of 0.0025 m/z units

Q9. (Note: This question intentionally assesses careful reading of units.) Which option correctly calculates 5 ppm error at m/z 500?

• 0.005 m/z units
• 0.05 m/z units
• 0.5 m/z units
• 0.0005 m/z units

Correct Answer: 0.0025 m/z units

Q10. What is a common cause of adduct formation in ESI mass spectra of pharmaceutical compounds?

• Chemical ionization with methane
• Reaction with carrier gas impurities
• Association with cations like Na+ or K+ in the sample/matrix
• Magnetic field fluctuations

Correct Answer: Association with cations like Na+ or K+ in the sample/matrix

Q11. Which mass analyzer is known for high resolving power and is based on electrostatic and magnetic fields in a double-focusing geometry?

• Quadrupole
• Ion trap
• Fourier transform ion cyclotron resonance (FT-ICR)
• Magnetic sector (double-focusing)

Correct Answer: Magnetic sector (double-focusing)

Q12. In quantitative LC-MS/MS for drugs, which scan mode provides the highest selectivity for targeted quantitation?

• Full-scan MS
• Selected ion monitoring (SIM)
• Selected reaction monitoring (SRM)/Multiple reaction monitoring (MRM)
• Product ion scan

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

Q13. What is the main advantage of high-resolution accurate-mass (HRAM) MS in metabolite identification?

• Faster chromatography
• Ability to determine elemental composition from exact mass and isotope pattern
• Lower operating vacuum requirements
• Higher ionization volatility

Correct Answer: Ability to determine elemental composition from exact mass and isotope pattern

Q14. Which statement about ion traps (3D or linear) is TRUE?

• They cannot perform MS/MS experiments
• They store ions and can sequentially isolate and fragment them for MSn experiments
• They separate ions strictly by time-of-flight
• They measure mass by cyclotron frequency

Correct Answer: They store ions and can sequentially isolate and fragment them for MSn experiments

Q15. What role does vacuum play in mass spectrometry?

• Increases ion-molecule collisions to promote fragmentation
• Reduces collisions with background gas to allow free ion flight and accurate m/z measurement
• Acts as a reagent gas for CI
• Maintains chromatographic separation inside the MS

Correct Answer: Reduces collisions with background gas to allow free ion flight and accurate m/z measurement

Q16. Which fragmentation rule is commonly used to rationalize cleavage in EI mass spectra of organic molecules?

• McLafferty rearrangement and alpha cleavage
• Homolytic cleavage only at aromatic rings
• Only proton transfer without bond cleavage
• Random fragmentation independent of structure

Correct Answer: McLafferty rearrangement and alpha cleavage

Q17. In LC-MS, what is a major reason to use isotopically labeled internal standards for quantitative assays?

• They improve chromatographic resolution
• They correct for matrix effects and ionization variability because they behave chemically like the analyte
• They increase the mass spectrometer vacuum
• They eliminate the need for calibration curves

Correct Answer: They correct for matrix effects and ionization variability because they behave chemically like the analyte

Q18. Which term best describes the phenomenon where a mass peak corresponds to an ion with multiple charges (e.g., +2, +3) commonly seen in ESI spectra of peptides?

• Isotopic fine structure
• Charge state distribution
• Neutral loss
• Adduct cluster

Correct Answer: Charge state distribution

Q19. What is the primary function of a quadrupole mass filter in triple-quadrupole (QQQ) MS used for pharmacokinetic assays?

• To provide very high resolving power like FT-ICR
• To act as a collision cell and also to selectively transmit particular m/z values
• To heat the sample to desorb analytes
• To detect ions with Faraday cup only

Correct Answer: To act as a collision cell and also to selectively transmit particular m/z values

Q20. Which practice improves mass accuracy and calibration stability in high-resolution MS instruments?

• Using only ambient air as collision gas
• Regular internal or external mass calibration with known reference compounds and stable instrument tuning
• Maximizing sample concentration regardless of detector saturation
• Avoiding maintenance of vacuum pumps

Correct Answer: Regular internal or external mass calibration with known reference compounds and stable instrument tuning

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