Time of flight analyzer MCQs With Answer

Time of flight analyzer MCQs With Answer

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Time of flight analyzer MCQs With Answer

Time-of-Flight (TOF) mass analyzers are central to modern pharmaceutical analytical techniques due to their high mass accuracy, rapid acquisition, and broad mass range. This quiz is tailored for M. Pharm students to strengthen conceptual and practical understanding of TOF principles, including flight dynamics, reflectron focusing, delayed extraction, orthogonal acceleration, calibration strategies, detector technologies, and common applications such as MALDI-TOF and ESI-TOF workflows. Emphasis is placed on resolution (m/Δm), mass accuracy (ppm), vacuum requirements, space-charge effects, and instrument configurations that enhance performance (e.g., Wiley–McLaren focusing, post-source decay, and IMS-TOF coupling). Each MCQ is designed to probe analytical reasoning relevant to pharmaceutical analysis—impurity profiling, metabolite identification, intact mass measurements, and exact mass confirmation—ensuring depth beyond definitions.

Q1. In a time-of-flight analyzer, how does ion flight time (t) scale with the mass-to-charge ratio (m/z)?

  • Flight time is inversely proportional to m/z
  • Flight time is directly proportional to m/z
  • Flight time is proportional to the square root of m/z
  • Flight time is independent of m/z

Correct Answer: Flight time is proportional to the square root of m/z

Q2. What is the primary function of a reflectron in TOF mass spectrometry?

  • Increase ionization efficiency
  • Corrects kinetic energy spread to improve resolution
  • Reduce matrix background in MALDI
  • Achieve tandem MS by collisional activation

Correct Answer: Corrects kinetic energy spread to improve resolution

Q3. In MALDI-TOF, why is delayed extraction used?

  • To lower laser power
  • To compensate for initial velocity and position spread of ions, sharpening peaks
  • To increase detector sensitivity
  • To filter out low m/z ions

Correct Answer: To compensate for initial velocity and position spread of ions, sharpening peaks

Q4. In mass spectrometry, resolving power (R) is typically expressed as:

  • R = Δm/m
  • R = m/Δm
  • R = m·Δm
  • R = Δm²/m

Correct Answer: R = m/Δm

Q5. If the acceleration voltage (V) is increased in a TOF analyzer, the flight time (t) for ions of a given m/z:

  • Increases linearly with V
  • Decreases as 1/√V
  • Is independent of V
  • Decreases linearly with V

Correct Answer: Decreases as 1/√V

Q6. Which detector is most commonly used in TOF mass spectrometers for high-speed ion detection?

  • Faraday cup
  • Electron multiplier dynode chain only
  • Microchannel plate detector
  • Photomultiplier tube

Correct Answer: Microchannel plate detector

Q7. TOF mass spectrometers typically operate at which vacuum level to minimize ion scattering?

  • ~1 mbar
  • ~10⁻² mbar
  • ~10⁻⁶ to 10⁻⁷ mbar
  • Atmospheric pressure

Correct Answer: ~10⁻⁶ to 10⁻⁷ mbar

Q8. What is the main advantage of orthogonal acceleration (oa-TOF) when coupled to ESI?

  • Enables use of continuous ion sources like ESI with improved duty cycle
  • Increases laser fluence in MALDI
  • Eliminates need for vacuum
  • Converts TOF into quadrupole

Correct Answer: Enables use of continuous ion sources like ESI with improved duty cycle

Q9. Wiley–McLaren time focusing in TOF refers to:

  • A type of detector
  • Two-stage extraction that focuses ions with different starting positions to arrive together
  • A calibration scheme using external standards
  • A reflectron operating mode

Correct Answer: Two-stage extraction that focuses ions with different starting positions to arrive together

Q10. For highest mass accuracy in TOF MS, which calibration approach is preferred?

  • External calibration at the beginning of the day
  • Internal calibration using reference ions in the same spectrum
  • Post-acquisition polynomial smoothing
  • Using the manufacturer’s factory constants

Correct Answer: Internal calibration using reference ions in the same spectrum

Q11. Modern reflectron TOF instruments typically achieve which mass accuracy with proper internal calibration?

  • ~100 ppm
  • 20–50 ppm
  • ≤2–5 ppm
  • 0.0001 ppm

Correct Answer: ≤2–5 ppm

Q12. Which laser wavelength is most commonly used in classical MALDI-TOF?

  • 1064 nm (Nd:YAG fundamental)
  • 532 nm (Nd:YAG second harmonic)
  • 337 nm (nitrogen laser)
  • 248 nm (KrF excimer)

Correct Answer: 337 nm (nitrogen laser)

Q13. A key pharmaceutical application ideally suited to TOF MS is:

  • Quantifying trace elements by atomic absorption
  • Accurate mass confirmation of drug metabolites and impurities
  • Separating chiral drugs without derivatization
  • Measuring NMR relaxation times

Correct Answer: Accurate mass confirmation of drug metabolites and impurities

Q14. In MALDI-TOF, post-source decay (PSD) primarily refers to:

  • Primary ionization in the source
  • Metastable fragmentation after acceleration in the field-free region
  • Collision-induced dissociation in a cell before TOF
  • In-source decay only for negative ions

Correct Answer: Metastable fragmentation after acceleration in the field-free region

Q15. What is the typical impact of increasing the flight path length (e.g., using a reflectron or multi-pass design)?

  • Increasing flight path length generally decreases resolution
  • Increasing flight path length generally increases resolution but may reduce sensitivity and increase acquisition time
  • Flight path length has no effect
  • Longer path causes lower mass accuracy

Correct Answer: Increasing flight path length generally increases resolution but may reduce sensitivity and increase acquisition time

Q16. Why is the duty cycle limited in a linear TOF with pulsed extraction for a continuous ion beam?

  • Because the detector is too slow
  • Because only ions present in the extraction region at the pulse are sampled; others are wasted
  • Because the reflectron blocks half the ions
  • Because laser frequency limits acquisition

Correct Answer: Because only ions present in the extraction region at the pulse are sampled; others are wasted

Q17. What is a common effect of space-charge in TOF mass spectrometry?

  • Results in narrower peaks and higher resolution
  • Causes peak broadening and mass shifts at high ion currents due to Coulomb repulsion
  • Eliminates need for calibration
  • Only affects negative ions

Correct Answer: Causes peak broadening and mass shifts at high ion currents due to Coulomb repulsion

Q18. Why is post-acceleration sometimes applied near the detector in TOF instruments?

  • To reduce flight time at low m/z
  • To increase ion impact energy on the MCP for better detection efficiency, especially of high-mass ions
  • To neutralize scattered ions before detection
  • To create a reflectron field

Correct Answer: To increase ion impact energy on the MCP for better detection efficiency, especially of high-mass ions

Q19. The instantaneous dynamic range per shot of a TOF MS with MCP detection is typically:

  • 10¹–10²
  • 10³–10⁴
  • 10⁶–10⁸
  • >10¹²

Correct Answer: 10³–10⁴

Q20. What is a key benefit of coupling ion mobility spectrometry (IMS) with TOF MS (e.g., IMS-QTOF or TIMS-TOF)?

  • Converts TOF into a low-resolution analyzer
  • Provides an orthogonal separation of ions by mobility before mass analysis, reducing chemical noise and resolving isomers
  • Eliminates need for a reflectron
  • Allows operation at atmospheric pressure throughout

Correct Answer: Provides an orthogonal separation of ions by mobility before mass analysis, reducing chemical noise and resolving isomers

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