Chemical Ionization MCQs With Answer offers a focused self-assessment tool for M. Pharm students studying Modern Pharmaceutical Analytical Techniques. Chemical ionization (CI) is a soft ionization method in mass spectrometry that enhances molecular ion information via controlled ion–molecule chemistry. These questions cover reagent gases (methane, isobutane, ammonia), reaction mechanisms (proton transfer, hydride abstraction, adduct formation), positive and negative CI modes, and practical method choices for pharmaceutical analysis. You will also assess understanding of gas-phase basicity/proton affinity, source conditions, spectrum interpretation, and applications such as GC–MS. Use this set to strengthen conceptual clarity and interpretive skills, ensuring confident selection of CI parameters for sensitive, selective, and reliable mass spectrometric measurements.
Q1. The defining feature of chemical ionization (CI) in mass spectrometry is that analyte ions are formed primarily by which process?
- Ion–molecule reactions between reagent gas ions and analyte molecules
- Direct electron impact on analyte molecules at 70 eV
- Photoionization using ultraviolet photons
- Matrix-assisted laser desorption
Correct Answer: Ion–molecule reactions between reagent gas ions and analyte molecules
Q2. Which gas is most commonly used as a reagent for positive chemical ionization in GC–MS?
- Methane
- Nitrogen
- Oxygen
- Xenon
Correct Answer: Methane
Q3. The dominant reagent ion produced in methane CI that efficiently protonates analytes is:
- CH5+
- C4H9+
- NH4+
- O2+
Correct Answer: CH5+
Q4. Among the following reagent gases, which generally provides the softest (least fragmenting) CI spectra?
- Ammonia
- Methane
- Isobutane
- Carbon dioxide
Correct Answer: Ammonia
Q5. In ammonia CI, for analytes with proton affinity lower than ammonia, the most abundant quasi-molecular ion is typically:
- [M+NH4]+
- [M+H]+
- M+•
- [M−H]−
Correct Answer: [M+NH4]+
Q6. Negative chemical ionization (NICI) is particularly sensitive for which class of compounds?
- Halogenated pesticides and explosives
- Saturated hydrocarbons lacking heteroatoms
- Alkali metal salts
- Noble gases
Correct Answer: Halogenated pesticides and explosives
Q7. Compared to electron ionization (EI), positive CI typically yields:
- Stronger [M+H]+ with reduced fragmentation
- Only radical cations M+• with extensive fragmentation
- Predominant dimer ions [2M+H]+ only
- No information about molecular weight
Correct Answer: Stronger [M+H]+ with reduced fragmentation
Q8. The typical total pressure of reagent gas in a CI source is on the order of:
- 0.1–2 Torr
- 10−6 Torr
- 100 Torr
- Atmospheric pressure (~760 Torr)
Correct Answer: 0.1–2 Torr
Q9. Proton transfer from NH4+ to an analyte M (forming MH+) will be thermodynamically favored when:
- The proton affinity of M is greater than that of NH3
- The ionization energy of M is lower than xenon
- The electron affinity of M is negative
- The molar mass of M exceeds 500 Da
Correct Answer: The proton affinity of M is greater than that of NH3
Q10. Hydride abstraction in positive CI, producing [M−H]+, is most commonly associated with which reagent ion?
- C4H9+ (from isobutane)
- CH5+ (from methane)
- NH4+ (from ammonia)
- Ar+
Correct Answer: C4H9+ (from isobutane)
Q11. Arrange the following reagent gases by decreasing extent of fragmentation in positive CI spectra:
- Methane > Isobutane > Ammonia
- Ammonia > Methane > Isobutane
- Isobutane > Methane > Ammonia
- Ammonia > Isobutane > Methane
Correct Answer: Methane > Isobutane > Ammonia
Q12. Which statement best describes adduct formation in ammonia CI?
- [M+NH4]+ adducts are common for analytes with lower proton affinity than ammonia
- Ammonia CI never forms adducts
- [M+O2]+ adducts dominate
- Adducts only occur in negative mode
Correct Answer: [M+NH4]+ adducts are common for analytes with lower proton affinity than ammonia
Q13. Why is CI often preferred over EI for thermally labile pharmaceuticals in GC–MS?
- CI reduces fragmentation through collisional cooling and soft ion–molecule reactions, aiding molecular weight assignment
- CI operates at lower source temperatures than the GC oven
- CI eliminates the need for derivatization in all cases
- CI produces identical spectra to library EI spectra
Correct Answer: CI reduces fragmentation through collisional cooling and soft ion–molecule reactions, aiding molecular weight assignment
Q14. In NICI, which ionization mechanism is most responsible for forming the molecular anion M− for nitroaromatic explosives?
- Resonance electron capture by M
- Dissociative electron attachment to reagent gas
- Proton abstraction by O2−
- Radiative recombination with NH4+
Correct Answer: Resonance electron capture by M
Q15. Which of the following sets lists typical positive CI ions?
- [M+H]+, [M+NH4]+, [M−H]+
- M+•, [M]−, [2M]•+
- [M+Na]+, [M+K]+, [M+Cl]−
- [M−]•−, [M−Cl]−, [M−H]−
Correct Answer: [M+H]+, [M+NH4]+, [M−H]+
Q16. For a target analyte with very high gas-phase basicity, which reagent gas is most likely to give an intense [M+H]+ with minimal fragmentation?
- Ammonia
- Methane
- Isobutane
- Helium
Correct Answer: Ammonia
Q17. Increasing the reagent gas pressure in a CI source generally leads to:
- Greater collisional cooling and reduced fragmentation
- Higher abundance of radical cations M+•
- Lower rate of ion–molecule reactions
- Complete suppression of adduct formation
Correct Answer: Greater collisional cooling and reduced fragmentation
Q18. The presence of isotope clusters around the quasi-molecular ion in CI (e.g., for organobromines) is most useful for:
- Confirming halogen content and exact molecular weight
- Determining collision cross-section
- Measuring chromatographic retention index
- Quantifying source pressure
Correct Answer: Confirming halogen content and exact molecular weight
Q19. Which pair correctly matches reagent gas with a predominant reagent ion?
- Isobutane — C4H9+
- Ammonia — CH5+
- Methane — NH4+
- Nitrogen — N2H+
Correct Answer: Isobutane — C4H9+
Q20. CI is most commonly implemented in which hyphenated technique for routine pharmaceutical analysis?
- GC–MS with a CI source
- MALDI–MS
- ICP–MS
- CE–MS with ESI
Correct Answer: GC–MS with a CI source

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