Chemical ionization MCQs With Answer

Chemical ionization MCQs With Answer

Chemical ionization (CI) is a soft ionization technique in mass spectrometry widely used for molecular weight determination and structural confirmation in pharmaceutical analysis. This focused MCQ set contains 20 carefully crafted questions for M.Pharm students enrolled in Advanced Instrumental Analysis (MPA 201T). Questions explore CI fundamentals, reagent gas chemistry (methane, isobutane, ammonia), ion-molecule mechanisms (proton transfer, charge exchange, adduct formation), source conditions, spectral interpretation, negative CI selectivity, and practical applications in GC-MS and tandem MS. Use these items to deepen conceptual understanding, prepare for exams, and reinforce decisions when applying CI in drug research and quality control.

Q1. What is the primary ionization mechanism in positive chemical ionization (CI) that leads to the common observation of [M+H]+?

• Electron impact fragmentation forming radical cations
• Proton transfer from reagent gas ions to the analyte producing [M+H]+
• Direct photoionization of the analyte
• Thermal decomposition followed by ionization

Correct Answer: Proton transfer from reagent gas ions to the analyte producing [M+H]+

Q2. Which set of reagent gases is most commonly used for positive chemical ionization in GC-MS?

• Argon, neon, krypton
• Methane, isobutane, ammonia
• Oxygen, nitrogen, helium
• Chlorine, bromine, iodine

Correct Answer: Methane, isobutane, ammonia

Q3. In methane CI, which ion is typically the dominant protonating reagent ion responsible for generating [M+H]+?

• CH4+• (methane radical cation)
• CH5+ (methanium ion)
• C2H5+ (ethylium ion)
• NH4+ (ammonium ion)

Correct Answer: CH5+ (methanium ion)

Q4. Compared with electron ionization (EI), a principal analytical advantage of chemical ionization is:

• Much higher fragmentation enabling detailed structural elucidation
• A complete absence of molecular ions
• Enhanced abundance of molecular (protonated) ions and reduced fragmentation
• Requirement for derivatization of all analytes

Correct Answer: Enhanced abundance of molecular (protonated) ions and reduced fragmentation

Q5. Which reagent gas often leads to formation of ammonium adducts such as [M+NH4]+ in CI spectra?

• Methane
• Isobutane
• Ammonia
• Argon

Correct Answer: Ammonia

Q6. Negative chemical ionization (NCI) is particularly sensitive to which class of compounds?

• Highly basic amines
• Neutral hydrocarbons with low electron affinity
• Electronegative compounds (e.g., halogenated, nitro-containing analytes)
• Metal ions and salts

Correct Answer: Electronegative compounds (e.g., halogenated, nitro-containing analytes)

Q7. Increasing reagent gas pressure in a CI source generally causes which effect on the mass spectrum?

• Decreased ion-molecule collisions and more fragmentation
• Increased ion-molecule reactions, favoring [M+H]+ formation and reducing fragmentation
• Elimination of molecular ions and only reagent gas peaks remain
• No effect on ion chemistry—only vacuum pump load changes

Correct Answer: Increased ion-molecule reactions, favoring [M+H]+ formation and reducing fragmentation

Q8. In the context of mass spectrometry, the term “soft ionization” (as applied to CI) refers to:

• Ionization producing abundant fragment ions but no molecular ions
• Minimal sample heating in the source
• Ionization that produces intact (protonated/adduct) molecular ions with limited fragmentation
• Use of low-voltage power supplies in the instrument

Correct Answer: Ionization that produces intact (protonated/adduct) molecular ions with limited fragmentation

Q9. Which spectral feature most reliably indicates that a CI experiment used a proton-transfer mechanism?

• Dominant peak corresponding to [M]•+ (molecular radical cation)
• Absence of any peaks above m/z 50
• Strong peak for [M+H]+ at one mass unit higher than the neutral molecular mass
• Prominent peaks for reagent gas clusters only

Correct Answer: Strong peak for [M+H]+ at one mass unit higher than the neutral molecular mass

Q10. Which type of pharmaceutical analyte is most likely to give an intense [M+H]+ in CI?

• Compounds with basic functional groups (amines, heterocycles) that readily accept a proton
• Inert saturated hydrocarbons with very low proton affinity
• Inorganic salts (e.g., NaCl)
• Large nonvolatile polymers only

Correct Answer: Compounds with basic functional groups (amines, heterocycles) that readily accept a proton

Q11. How does increasing source temperature in a CI source typically affect adduct formation and fragmentation?

• Higher temperature increases adduct clustering and reduces fragmentation
• Higher temperature reduces cluster/adduct formation and may increase fragmentation
• Temperature has no effect on CI reactions
• Higher temperature converts CI to EI-like ionization instantly

Correct Answer: Higher temperature reduces cluster/adduct formation and may increase fragmentation

Q12. Which reagent gas is generally considered to produce the softest ionization, frequently yielding stable adducts and minimal fragmentation?

• Methane
• Isobutane
• Ammonia
• Helium

Correct Answer: Ammonia

Q13. In positive CI, the common notation for the observed protonated molecular ion is:

• [M]•+
• [M+H]+
• [M−H]−
• [M++NH4]

Correct Answer: [M+H]+

Q14. Why is CI particularly useful in GC-MS analysis of drug candidates for M.Pharm applications?

• It fragments compounds into very small ions that are easier to quantify
• It allows clear molecular weight determination by producing prominent [M+H]+ or adduct peaks with reduced fragmentation
• It eliminates the need for chromatographic separation
• It is only used for inorganic analysis, not organics

Correct Answer: It allows clear molecular weight determination by producing prominent [M+H]+ or adduct peaks with reduced fragmentation

Q15. What is produced when charge exchange, rather than proton transfer, dominates the CI ion-molecule reaction?

• Protonated molecule [M+H]+
• Molecular radical cation [M]•+
• Negative ion [M−H]−
• Cluster ion [M+reagent]+

Correct Answer: Molecular radical cation [M]•+

Q16. To favor formation of an ammonium adduct [M+NH4]+ during CI, which combination of conditions is most appropriate?

• Use methane reagent gas at very high source temperature
• Use ammonia reagent gas with moderate-to-high reagent gas pressure and relatively low source temperature
• Use helium reagent gas at low pressure
• Use isobutane and turn off the source heater

Correct Answer: Use ammonia reagent gas with moderate-to-high reagent gas pressure and relatively low source temperature

Q17. In tandem mass spectrometry (MS/MS), why is CI often used as an ionization step before collision-induced dissociation (CID)?

• Because CI eliminates all precursor ions so CID is unnecessary
• CI provides abundant, intact protonated molecular precursors ([M+H]+) that can be selectively fragmented by CID for structural elucidation
• CI generates only negative ions, which are required for CID
• CI produces continuous neutrals ideal for CID

Correct Answer: CI provides abundant, intact protonated molecular precursors ([M+H]+) that can be selectively fragmented by CID for structural elucidation

Q18. A distinctive feature of negative CI (NCI) spectra for halogenated pharmaceuticals is:

• Uniform strong [M+H]+ peaks irrespective of electronegativity
• Selective formation of negative ions such as [M]− or [M]−• or even [M−H]− with high sensitivity for halogenated species
• Production of only reagent gas ions with no analyte signal
• Complete suppression of molecular ions and only fragments from the carrier gas

Correct Answer: Selective formation of negative ions such as [M]− or [M]−• or even [M−H]− with high sensitivity for halogenated species

Q19. Which of the following statements about chemical ionization is FALSE?

• CI typically produces softer spectra with more prominent molecular ions than EI
• CI employs reagent gases to create reagent ions that transfer charge or protons
• CI always produces only radical cations and never protonated molecules
• Reagent gas selection influences the extent of fragmentation and adduct formation in CI

Correct Answer: CI always produces only radical cations and never protonated molecules

Q20. Which instrument parameter most directly controls the frequency of ion-molecule collisions in a chemical ionization source?

• Electron multiplier voltage
• Reagent gas (source) pressure
• Quadrupole mass filter resolution setting
• Injector split ratio on the GC

Correct Answer: Reagent gas (source) pressure

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