Ionization techniques – Chemical ionization MCQs With Answer

Ionization techniques – Chemical ionization MCQs With Answer

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Introduction: Chemical ionization (CI) is a key ionization technique in mass spectrometry that B.Pharm students must master for drug analysis and structural elucidation. CI is a soft ionization method that uses a reagent gas (e.g., methane, isobutane, ammonia) ionized by electrons to produce reagent ions which transfer charge or protons to analyte molecules. Compared with electron ionization (EI), CI produces prominent quasi-molecular ions ([M+H]+, [M+NH4]+ or [M−H]−) with reduced fragmentation, aiding accurate molecular weight determination. Understanding reagent ion chemistry, proton affinity, adduct formation, spectral interpretation, and practical parameters (source pressure, gas choice) is essential for pharmaceutical analysis.
Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary advantage of chemical ionization (CI) over electron ionization (EI) in mass spectrometry for pharmaceutical compounds?

  • Higher internal energy leading to more fragmentation
  • Production of quasi-molecular ions with reduced fragmentation
  • Requirement for larger sample amounts
  • Less selectivity for molecular weight determination

Correct Answer: Production of quasi-molecular ions with reduced fragmentation

Q2. In positive chemical ionization (PCI), which type of ion is most commonly observed for neutral organic molecules?

  • [M]•+
  • [M+H]+
  • [M−H]−
  • [M+O2]+

Correct Answer: [M+H]+

Q3. Which reagent gas is commonly used in CI when softer ionization and enhanced proton transfer are desired?

  • Oxygen
  • Methane
  • Neon
  • Chlorine

Correct Answer: Methane

Q4. How are reagent ions generated in chemical ionization?

  • By direct UV photoionization of the analyte
  • By electron ionization of the reagent gas producing primary reagent ions
  • By laser desorption of the sample
  • By thermal decomposition of analyte molecules

Correct Answer: By electron ionization of the reagent gas producing primary reagent ions

Q5. Which process best describes proton transfer in CI that forms [M+H]+?

  • M + e− → M−
  • R+ + M → RH+ + M
  • R+ + M → [M+H]+ + R•
  • M → M•+ + e−

Correct Answer: R+ + M → [M+H]+ + R•

Q6. Which reagent gas often produces NH4+ ions that can form [M+NH4]+ adducts in CI?

  • Isobutane
  • Ammonia
  • Methane
  • Argon

Correct Answer: Ammonia

Q7. Negative chemical ionization (NCI) is particularly useful for detecting which type of pharmaceutical analytes?

  • Highly basic compounds with high proton affinity
  • Electron-capturing electronegative compounds (e.g., halogenated)
  • Neutral nonpolar hydrocarbons
  • Metal complexes

Correct Answer: Electron-capturing electronegative compounds (e.g., halogenated)

Q8. Which of the following is a common negative CI ion observed for acidic molecules?

  • [M+H]+
  • [M]•+
  • [M−H]−
  • [M+NH4]+

Correct Answer: [M−H]−

Q9. How does increasing reagent gas pressure in the CI source generally affect ionization?

  • Decreases reagent ion generation and reduces [M+H]+ formation
  • Increases collisional cooling and favors softer ionization with more adduct formation
  • Causes complete fragmentation to radicals
  • Converts CI into EI-like behavior

Correct Answer: Increases collisional cooling and favors softer ionization with more adduct formation

Q10. Which statement correctly contrasts CI and EI spectra for the same compound?

  • CI shows more extensive fragmentation than EI
  • CI generally lacks molecular-related peaks while EI shows clear [M+H]+
  • CI often shows prominent quasi-molecular ions, EI often shows abundant fragment ions
  • CI cannot be used for molecular weight determination

Correct Answer: CI often shows prominent quasi-molecular ions, EI often shows abundant fragment ions

Q11. Which property of an analyte most strongly predicts its tendency to form [M+H]+ in CI?

  • Vapor pressure
  • Proton affinity (gas-phase basicity)
  • Melting point
  • Optical rotation

Correct Answer: Proton affinity (gas-phase basicity)

Q12. In CI using methane, which primary reagent ion is commonly involved in creating product ions?

  • CH5+
  • O2+
  • N2+
  • Ar+

Correct Answer: CH5+

Q13. Which adduct ion is typically observed when ammonium-containing reagent gas or source additives are present?

  • [M−H]−
  • [M+NH4]+
  • [M•+]
  • [M+Cl]−

Correct Answer: [M+NH4]+

Q14. Why is CI considered a “soft” ionization technique?

  • Because it uses very high electron energies that break all bonds
  • Because reagent ions transfer charge or protons with lower internal energy input, producing less fragmentation
  • Because it only ionizes metals
  • Because it works only at cryogenic temperatures

Correct Answer: Because reagent ions transfer charge or protons with lower internal energy input, producing less fragmentation

Q15. Which CI outcome helps directly determine the molecular weight of a drug molecule?

  • Observation of multiple low-mass fragments only
  • Detection of quasi-molecular peaks such as [M+H]+ or [M+NH4]+
  • Only seeing reagent gas peaks
  • Complete decomposition to elemental ions

Correct Answer: Detection of quasi-molecular peaks such as [M+H]+ or [M+NH4]+

Q16. Which factor can increase fragmentation in CI spectra, reducing the softness?

  • Lowering electron energy for reagent ion production
  • Using a reagent gas with very low proton affinity
  • Increasing source temperature or electron energy
  • Adding ammonium acetate to the sample

Correct Answer: Increasing source temperature or electron energy

Q17. In the mechanism of charge exchange CI, which event occurs?

  • Reagent radical cation transfers an electron to the analyte producing M•+
  • Proton transfer to form [M+H]+ exclusively
  • Analyte fragments without ion formation
  • Neutral reagent gas directly attaches to analyte

Correct Answer: Reagent radical cation transfers an electron to the analyte producing M•+

Q18. Which CI reagent gas is commonly chosen for minimal fragmentation and good molecular ion sensitivity for polar drug molecules?

  • Ammonia
  • Neon
  • Krypton
  • Oxygen

Correct Answer: Ammonia

Q19. What spectral feature indicates formation of an ammonium adduct [M+NH4]+ rather than simple protonation?

  • A peak at m/z equal to molecular mass minus 1
  • A peak 18 Da higher than the neutral molecular mass
  • A radical cation peak at exact molecular mass
  • No peaks near the molecular mass

Correct Answer: A peak 18 Da higher than the neutral molecular mass

Q20. When analyzing thermally labile pharmaceuticals, why might CI coupled to GC be preferred over EI-GC-MS?

  • CI increases thermal decomposition
  • CI provides softer ionization and preserves molecular ions for labile compounds
  • CI requires much higher column temperatures
  • CI is incompatible with GC interfaces

Correct Answer: CI provides softer ionization and preserves molecular ions for labile compounds

Q21. Which statement about metastable ions in CI spectra is true?

  • Metastable ions cannot be detected in mass spectrometers
  • Metastable ions result from in-flight fragmentation and can provide structural information
  • Metastable ions are only produced in negative CI
  • Metastable ions indicate instrument malfunction

Correct Answer: Metastable ions result from in-flight fragmentation and can provide structural information

Q22. In a CI experiment, what role does the ion source temperature mainly play?

  • It solely determines the m/z calibration
  • It affects sample vaporization, reagent gas chemistry, and degree of fragmentation
  • It converts positive ions to negative ions
  • It eliminates the need for a mass analyzer

Correct Answer: It affects sample vaporization, reagent gas chemistry, and degree of fragmentation

Q23. How can CI be tuned to favor formation of [M+H]+ over adducts?

  • Introduce ammonium salts into the source
  • Use a reagent gas and conditions that promote proton transfer (e.g., methane, optimized pressure)
  • Increase the amount of water in the source
  • Lower the proton affinity of the analyte

Correct Answer: Use a reagent gas and conditions that promote proton transfer (e.g., methane, optimized pressure)

Q24. Which mass spectral peak would most directly confirm the nominal molecular weight of a neutral drug using PCI?

  • Most intense low-mass fragment
  • [M+H]+ peak at (M + 1) m/z
  • Only reagent gas peaks
  • Baseline noise

Correct Answer: [M+H]+ peak at (M + 1) m/z

Q25. Which of the following analyte properties makes negative CI more sensitive than positive CI?

  • High gas-phase basicity
  • Presence of electronegative functional groups with high electron affinity
  • Very low molecular weight
  • Strong UV absorption

Correct Answer: Presence of electronegative functional groups with high electron affinity

Q26. In CI, what is the common origin of the CH5+ ion when methane is used?

  • Direct ionization of the analyte
  • Reaction of CH4+• with excess CH4 to produce CH5+
  • Thermal decomposition of the column stationary phase
  • Electron capture by methane producing CH5−

Correct Answer: Reaction of CH4+• with excess CH4 to produce CH5+

Q27. Which analytical application in pharmaceutical analysis benefits most from CI?

  • Accurate molecular weight determination of drug metabolites and impurities
  • Fluorescence spectroscopy of tablets
  • Determining optical isomer ratios
  • Measuring tablet hardness

Correct Answer: Accurate molecular weight determination of drug metabolites and impurities

Q28. What effect does a high proton affinity reagent gas have on CI proton transfer reactions?

  • It prevents reagent ion formation entirely
  • It may compete with analyte for protons, reducing [M+H]+ formation
  • It always increases fragmentation
  • It converts CI into an electron capture process

Correct Answer: It may compete with analyte for protons, reducing [M+H]+ formation

Q29. Which observation suggests that a CI spectrum contains a charge-exchange (M•+) ion rather than a protonated molecule?

  • Peak at m/z = M + 1
  • Peak at m/z equal to the exact molecular mass (M) with radical cation behavior
  • Only negative ions observed
  • No peaks near the molecular mass

Correct Answer: Peak at m/z equal to the exact molecular mass (M) with radical cation behavior

Q30. When interpreting CI spectra of pharmaceuticals, which combined approach improves confident structural assignment?

  • Relying solely on base peak intensity
  • Combining quasi-molecular ion identification, knowledge of reagent chemistry, and fragmentation pattern analysis
  • Only measuring retention time
  • Ignoring adduct peaks

Correct Answer: Combining quasi-molecular ion identification, knowledge of reagent chemistry, and fragmentation pattern analysis

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