Mass spectrometry instrumentation MCQs With Answer

Mass spectrometry instrumentation MCQs With Answer

This quiz collection is tailored for M.Pharm students studying Advanced Instrumental Analysis (MPA 201T). It focuses specifically on mass spectrometry instrumentation — covering ionization techniques, mass analyzers, detectors, vacuum systems, ion optics, tandem MS and practical aspects such as sensitivity, resolution and quantitative modes. Questions are designed to deepen conceptual understanding and application skills necessary for pharmaceutical analysis, including peptide/protein analysis, small-molecule quantification and method troubleshooting. Each question includes four options and a clear correct answer to help you test and reinforce learning, prepare for exams and perform better in practical laboratory work involving mass spectrometers.

Q1. Which ionization technique is most suitable for producing multiply charged ions of intact proteins, enabling analysis of high molecular weight species by mass analyzers with limited m/z range?

• Electron Ionization (EI)
• Matrix-Assisted Laser Desorption/Ionization (MALDI)
• Electrospray Ionization (ESI)
• Chemical Ionization (CI)

Correct Answer: Electrospray Ionization (ESI)

Q2. In a quadrupole mass analyzer, what parameter is primarily adjusted to selectively transmit ions of a given mass-to-charge ratio (m/z)?

• The magnetic field strength
• The radiofrequency (RF) and direct current (DC) voltages
• The time delay between ion pulses
• The energy of the ionizing electrons

Correct Answer: The radiofrequency (RF) and direct current (DC) voltages

Q3. Which detector type is most commonly used in modern mass spectrometers for counting single ions with high gain and fast response?

• Faraday cup
• Electron multiplier (dynode)
• Thermal conductivity detector
• Flame ionization detector

Correct Answer: Electron multiplier (dynode)

Q4. What is the main advantage of Time-of-Flight (TOF) mass analyzers compared to single quadrupoles?

• Intrinsic ability to perform MS/MS without collision cell
• Unlimited mass range with very high mass accuracy and fast acquisition
• Superior ion trapping for long-term storage
• Higher chemical ionization efficiency for volatile compounds

Correct Answer: Unlimited mass range with very high mass accuracy and fast acquisition

Q5. Which statement best describes resolution (resolving power) in mass spectrometry?

• Resolution is the percentage of ions transmitted through the analyzer
• Resolution is m/Δm, where Δm is the smallest mass difference that can be separated at mass m
• Resolution is the absolute mass error in Daltons
• Resolution equals the number of ions detected per second

Correct Answer: Resolution is m/Δm, where Δm is the smallest mass difference that can be separated at mass m

Q6. Which fragmentation technique is most commonly used in tandem mass spectrometry (MS/MS) within a collision cell to induce collision-induced dissociation (CID)?

• Electron capture dissociation (ECD)
• High-energy collision-induced dissociation using inert gas in a collision cell
• MALDI post-source decay (PSD)
• Surface-induced dissociation (SID)

Correct Answer: High-energy collision-induced dissociation using inert gas in a collision cell

Q7. Which mass analyzer provides the highest mass resolving power and can achieve sub-ppm mass accuracy, making it ideal for elemental composition determination?

• Single quadrupole
• Ion trap
• Fourier transform ion cyclotron resonance (FT-ICR)
• Magnetic sector with low resolution

Correct Answer: Fourier transform ion cyclotron resonance (FT-ICR)

Q8. In electrospray ionization (ESI), which factor most directly contributes to ion suppression in complex biological samples?

• High vacuum level in the mass analyzer
• Co-eluting matrix components that compete for charge and surface at the droplet
• The m/z range of the analyzer
• Voltage applied to the detector

Correct Answer: Co-eluting matrix components that compete for charge and surface at the droplet

Q9. What is the primary role of the skimmer/ion funnel interface in LC–MS with ESI?

• To fragment ions before mass analysis
• To remove neutral solvent and focus ions from atmospheric pressure into the vacuum
• To measure ion current as a bulk signal
• To generate a magnetic field for ion separation

Correct Answer: To remove neutral solvent and focus ions from atmospheric pressure into the vacuum

Q10. Which of the following best describes resolution trade-off in Orbitrap mass analyzers?

• Longer transient detection yields higher resolving power but slower scan speed
• Shorter transients give higher resolution and higher mass accuracy
• Resolution is independent of transient length and only depends on ion current
• Resolution decreases as m/z decreases

Correct Answer: Longer transient detection yields higher resolving power but slower scan speed

Q11. Which scan mode is typically used in triple quadrupole instruments for highly sensitive and selective quantification of known compounds?

• Full-scan MS
• Selected Reaction Monitoring (SRM) or Multiple Reaction Monitoring (MRM)
• Neutral loss scan
• Precursor ion scan

Correct Answer: Selected Reaction Monitoring (SRM) or Multiple Reaction Monitoring (MRM)

Q12. Which phenomenon is described by ‘space-charge effects’ inside ion traps or analyzers?

• Signal enhancement due to increased ion focusing
• Distortion of electric fields and reduced performance due to high ion density
• Complete neutralization of ions by residual gas
• Spontaneous fragmentation of ions at low m/z

Correct Answer: Distortion of electric fields and reduced performance due to high ion density

Q13. What is the principal advantage of high-resolution accurate-mass (HRAM) instruments in pharmaceutical analysis?

• They eliminate the need for chromatography entirely
• They allow exact elemental composition assignment and improved selectivity for complex matrices
• They operate without a vacuum system
• They always provide higher sensitivity than triple quadrupoles in all assays

Correct Answer: They allow exact elemental composition assignment and improved selectivity for complex matrices

Q14. Which ionization method is most appropriate for analyzing non-volatile, high-mass biomolecules from solid samples with minimal fragmentation?

• Electron Ionization (EI)
• Matrix-Assisted Laser Desorption/Ionization (MALDI)
• Atmospheric Pressure Chemical Ionization (APCI)
• Chemical Ionization (CI)

Correct Answer: Matrix-Assisted Laser Desorption/Ionization (MALDI)

Q15. In mass spectrometry, what does ‘mass accuracy’ refer to?

• The ratio of signal to noise for a peak
• The closeness of the measured m/z value to the true or theoretical m/z value
• The minimum m/z detectable by the instrument
• The speed at which spectra are acquired

Correct Answer: The closeness of the measured m/z value to the true or theoretical m/z value

Q16. Which instrument configuration is typically used for high-throughput quantitative bioanalysis in regulated pharmaceutical labs?

• Orbitrap with MALDI source
• Triple quadrupole (QQQ) with ESI source in MRM mode
• FT-ICR without chromatography
• Single quadrupole with electron impact ionization

Correct Answer: Triple quadrupole (QQQ) with ESI source in MRM mode

Q17. What is a common cause of adduct formation (e.g., [M+Na]+, [M+K]+) in ESI mass spectra and how is it minimized?

• High vacuum causes adducts; increase pressure to minimize
• Contaminant cations in solvents or glassware; use high-purity solvents and add acid or ammonium acetate to favor protonation
• Laser intensity fluctuations; stabilize laser power
• Magnetic field interference; shield the instrument

Correct Answer: Contaminant cations in solvents or glassware; use high-purity solvents and add acid or ammonium acetate to favor protonation

Q18. Which of the following best describes the role of collision energy in MS/MS experiments?

• Collision energy determines the m/z detection limit of the analyzer
• Collision energy controls fragmentation pathways and can be tuned to obtain structural information
• Collision energy reduces vacuum requirements
• Collision energy is unrelated to ion fragmentation

Correct Answer: Collision energy controls fragmentation pathways and can be tuned to obtain structural information

Q19. What advantage does an ion mobility spectrometry (IMS) stage coupled before MS provide?

• IMS decreases ion transmission to simplify spectra
• IMS separates ions by their size, shape and charge (collision cross-section), adding an orthogonal separation dimension
• IMS replaces the need for ionization
• IMS increases the vacuum pressure in the analyzer

Correct Answer: IMS separates ions by their size, shape and charge (collision cross-section), adding an orthogonal separation dimension

Q20. When calibrating a high-resolution mass spectrometer for accurate mass measurements, which practice is most appropriate?

• Use a single low-mass calibration point only
• Perform external calibration once and never recalibrate
• Use multiple calibration points across the mass range and perform regular internal or external calibration checks
• Calibrate using random sample peaks without known exact masses

Correct Answer: Use multiple calibration points across the mass range and perform regular internal or external calibration checks

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