Mass analyzers – Time-of-Flight and Quadrupole MCQs With Answer

Introduction: Mass analyzers are central to mass spectrometry in pharmaceutical analysis. Time-of-Flight (TOF) and Quadrupole analyzers offer complementary strengths for B. Pharm students: TOF provides high resolution, wide mass range, and rapid acquisition using pulsed ion beams and flight-time measurement, while Quadrupole analyzers use oscillating RF/DC fields to filter ions by mass-to-charge ratio (m/z) with excellent quantitative performance and robustness. Understanding ion optics, resolution, accuracy, duty cycle, calibration, and coupling to ionization sources (ESI, MALDI) is essential for drug discovery, impurity profiling, and bioanalysis. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What fundamental principle allows a Time-of-Flight (TOF) mass analyzer to separate ions?

• Ions are separated by their chemical reactivity in a gas phase column
• Ions are separated by their flight time, which depends on mass-to-charge ratio
• Ions are separated by differential diffusion rates through a membrane
• Ions are separated by colorimetric detection after fragmentation

Correct Answer: Ions are separated by their flight time, which depends on mass-to-charge ratio

Q2. Which ionization technique is most commonly paired with TOF for large biomolecules in pharmaceutical analysis?

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

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

Q3. How does a quadrupole mass filter select ions of a specific m/z?

• By measuring ion flight time in a field-free region
• By using magnetic fields to bend ion trajectories
• By applying specific combinations of RF and DC voltages to create stability regions
• By detecting ions using optical absorption

Correct Answer: By applying specific combinations of RF and DC voltages to create stability regions

Q4. Which feature is a key advantage of TOF analyzers over single quadrupoles?

• Lower mass range
• Higher resolution and faster acquisition rates
• Better ion trapping for MS/MS experiments
• Cheaper maintenance costs in all cases

Correct Answer: Higher resolution and faster acquisition rates

Q5. In a reflectron TOF, what purpose does the reflectron serve?

• It increases ionization efficiency
• It focuses ions of different kinetic energies to improve resolution
• It neutralizes ions before detection
• It converts ions into photons for optical detection

Correct Answer: It focuses ions of different kinetic energies to improve resolution

Q6. Which parameter defines the resolving power of a mass analyzer?

• m/Δm (mass divided by mass peak width at a specified peak height)
• Ionization potential of the sample
• Flow rate of the carrier gas
• Detector plate area

Correct Answer: m/Δm (mass divided by mass peak width at a specified peak height)

Q7. What is the primary limitation of a single quadrupole for qualitative high-resolution mass measurement?

• Insensitivity to low concentration analytes
• Inability to provide high mass resolving power compared to TOF
• Excessive mass range beyond practical use
• Excessively slow scan rates

Correct Answer: Inability to provide high mass resolving power compared to TOF

Q8. Which detection system is commonly used with TOF analyzers for fast ion detection?

• Thermal conductivity detector
• Microchannel plate (MCP) detector
• Flame ionization detector
• Photomultiplier tube for visible light

Correct Answer: Microchannel plate (MCP) detector

Q9. What does “orthogonal acceleration” in TOF refer to?

• Acceleration of ions along the same axis as the ion source
• Acceleration of ions at right angles to the initial ion beam to improve timing precision
• Acceleration using magnetic fields instead of electric fields
• Acceleration only used in quadrupole instruments

Correct Answer: Acceleration of ions at right angles to the initial ion beam to improve timing precision

Q10. Which operational mode of a quadrupole is commonly used for quantitative drug analysis?

• Full mass spectrum acquisition at the highest resolution
• Selected ion monitoring (SIM) or multiple reaction monitoring (MRM) in tandem setups
• Neutral loss scanning
• Time-resolved fluorescence detection

Correct Answer: Selected ion monitoring (SIM) or multiple reaction monitoring (MRM) in tandem setups

Q11. How does space charge effect influence TOF performance?

• It enhances resolution by compacting ion packets
• Excess ion population leads to broadening of peak widths and reduced mass accuracy
• It neutralizes ions, increasing signal intensity
• It causes ions to fluoresce for optical detection

Correct Answer: Excess ion population leads to broadening of peak widths and reduced mass accuracy

Q12. Which factor improves mass accuracy in both TOF and quadrupole systems?

• Poor vacuum conditions
• Regular calibration with known mass standards
• Using the highest possible ion beam current without limit
• Lowering the ionization voltage to zero

Correct Answer: Regular calibration with known mass standards

Q13. Why is coupling LC to a quadrupole advantageous in pharmaceutical assays?

• It eliminates the need for ionization
• It provides chromatographic separation with selective mass filtering for sensitive quantitation
• It converts quadrupole into a TOF analyzer
• It prevents any matrix effects entirely

Correct Answer: It provides chromatographic separation with selective mass filtering for sensitive quantitation

Q14. Which of the following best describes duty cycle in TOF instruments?

• The percentage of ions neutralized before detection
• The fraction of ions actually measured per pulse due to pulsed ion extraction and detection timing
• The power consumption of the detector per run
• The time needed to pump down the vacuum chamber

Correct Answer: The fraction of ions actually measured per pulse due to pulsed ion extraction and detection timing

Q15. In a quadrupole, what happens when RF and DC voltages are tuned to an unstable region for a given m/z?

• Ions of that m/z are transmitted with higher efficiency
• Ions of that m/z have unstable trajectories and are ejected or lost
• Ions become neutral and are detected as neutrals
• The quadrupole converts to a reflector for TOF operation

Correct Answer: Ions of that m/z have unstable trajectories and are ejected or lost

Q16. What is a common use of TOF-MS in pharmaceutical research?

• Only routine quantitation of small molecules at low resolution
• High-throughput accurate mass measurement for identification of unknown metabolites
• Replacing HPLC columns for separation
• Measuring thermal properties of solid drugs

Correct Answer: High-throughput accurate mass measurement for identification of unknown metabolites

Q17. Why are reflectron TOF instruments better at resolving isobaric peaks than linear TOF?

• Reflectron reduces kinetic energy spread by time-focusing, narrowing peaks
• Reflectron increases ionization cross-section dramatically
• Reflectron uses magnetic fields which linear TOF does not
• Reflectron eliminates the need for vacuum

Correct Answer: Reflectron reduces kinetic energy spread by time-focusing, narrowing peaks

Q18. For a quadrupole used as a mass filter, increasing the RF amplitude while holding DC constant generally:

• Has no effect on ion transmission
• Shifts stability zones, allowing transmission of higher m/z ions
• Converts transmitted ions into neutral species
• Improves chromatographic separation

Correct Answer: Shifts stability zones, allowing transmission of higher m/z ions

Q19. What is the effect of pulsed ionization on TOF-MS sensitivity and resolution?

• Pulsed ionization degrades resolution but always increases sensitivity
• Pulsed ionization enables precise time zero, improving resolution and synchronized detection, but duty cycle may reduce sensitivity
• Pulsed ionization only affects quadrupole instruments
• Pulsed ionization eliminates the need for detectors

Correct Answer: Pulsed ionization enables precise time zero, improving resolution and synchronized detection, but duty cycle may reduce sensitivity

Q20. Which statement about scan speed is true when comparing quadrupoles and TOF?

• Quadrupoles scan full mass ranges faster than TOF
• TOF acquires full mass spectra rapidly in microseconds, offering high scan speed for pulsed experiments
• Both have identical scan speeds regardless of settings
• TOF requires longer scan times because ions are trapped for seconds

Correct Answer: TOF acquires full mass spectra rapidly in microseconds, offering high scan speed for pulsed experiments

Q21. Which term best describes the quadrupole’s typical mass resolution performance?

• Ultra-high resolution (>100,000)
• Low to unit mass resolution suitable for targeted quantitation
• Optical resolution dependent on lamps
• Infinite resolution due to dynamic fields

Correct Answer: Low to unit mass resolution suitable for targeted quantitation

Q22. How does the mass range of TOF compare to that of a quadrupole?

• TOF typically offers a wider mass range suitable for large biomolecules, while quadrupoles are optimized for low-to-moderate m/z
• Quadrupoles always handle higher masses than TOF
• Both have identical mass ranges by design
• Neither can analyze m/z above 500

Correct Answer: TOF typically offers a wider mass range suitable for large biomolecules, while quadrupoles are optimized for low-to-moderate m/z

Q23. In tandem MS (MS/MS), a quadrupole is often used as:

• A detector that converts ions to photons
• A mass filter to select precursor ions before fragmentation
• An ion source to create ions from neutrals
• A vacuum pump for the analyzer chamber

Correct Answer: A mass filter to select precursor ions before fragmentation

Q24. What is one common cause of reduced resolution in TOF instruments?

• Perfect vacuum conditions
• Kinetic energy spread of ions due to imperfect ion extraction
• Use of reflectron focusing
• Using calibrated mass standards

Correct Answer: Kinetic energy spread of ions due to imperfect ion extraction

Q25. Which maintenance aspect is particularly important for quadrupole longevity?

• Regular replacement of laser matrix
• Keeping electrode surfaces clean and maintaining stable RF/DC supplies
• Heating the quadrupole to high temperatures daily
• Immersing electrodes in solvent after each run

Correct Answer: Keeping electrode surfaces clean and maintaining stable RF/DC supplies

Q26. How does MALDI-TOF benefit peptide and protein analysis in pharma?

• MALDI prevents ionization of large biomolecules
• MALDI-TOF provides soft ionization with minimal fragmentation and accurate mass for intact biomolecules
• MALDI-TOF is only used for inorganic compounds
• MALDI-TOF uses quadrupole filtration exclusively

Correct Answer: MALDI-TOF provides soft ionization with minimal fragmentation and accurate mass for intact biomolecules

Q27. What role does flight path length play in TOF resolution?

• Longer flight path generally improves resolution by increasing separation of flight times for different m/z
• Flight path length has no impact on resolution
• Shorter flight paths always yield higher resolution
• Flight path length only affects quadrupole filters

Correct Answer: Longer flight path generally improves resolution by increasing separation of flight times for different m/z

Q28. Which phenomenon is most important when performing accurate mass measurements with TOF?

• Ambient room temperature on the operator
• Frequent mass calibration and control of electric fields and flight-time zero offset
• Using the highest ion current possible without calibration
• Choosing the darkest matrix in MALDI

Correct Answer: Frequent mass calibration and control of electric fields and flight-time zero offset

Q29. In LC–quadrupole–MS workflows for drug quantitation, what is the advantage of MRM in a triple quadrupole?

• MRM increases background noise to enhance peaks
• MRM provides high sensitivity and selectivity by monitoring specific precursor-to-product ion transitions
• MRM eliminates the need for sample preparation entirely
• MRM converts quadrupoles into TOF instruments

Correct Answer: MRM provides high sensitivity and selectivity by monitoring specific precursor-to-product ion transitions

Q30. Which statement best contrasts TOF and quadrupole analyzers for B. Pharm applications?

• TOF is universally superior to quadrupole for all assays
• Quadrupole offers robust, sensitive targeted quantitation; TOF offers wide mass range and accurate mass for identification and discovery
• Both analyzers operate identically and are chosen randomly
• Quadrupole is only useful for gas chromatography coupling, not LC

Correct Answer: Quadrupole offers robust, sensitive targeted quantitation; TOF offers wide mass range and accurate mass for identification and discovery

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