APCI ionization MCQs With Answer

APCI ionization MCQs With Answer

by

APCI Ionization MCQs With Answer

Atmospheric Pressure Chemical Ionization (APCI) is a cornerstone interface in LC–MS for M. Pharm students studying Modern Pharmaceutical Analytical Techniques. This blog presents a focused set of MCQs with answers to help you master APCI fundamentals—its corona discharge-driven gas-phase chemistry, source design, and practical method development. You will explore reagent ions, proton and charge transfer mechanisms, parameter optimization (vaporizer temperature, gas flows, corona current), and comparisons with ESI and APPI. Emphasis is placed on analyte suitability, mobile-phase effects, matrix suppression, and troubleshooting for quantitative bioanalysis. Use these questions to reinforce key concepts and develop the practical insight needed to select, optimize, and critically evaluate APCI methods in pharmaceutical research.

Q1. Which statement best describes the principle of APCI in LC–MS?

  • Ionization occurs via gas-phase ion–molecule reactions initiated by a corona discharge at atmospheric pressure
  • Charged droplets undergo Coulombic fission until bare ions are released
  • Photons from a UV lamp ionize dopant molecules that transfer charge to analytes
  • Ions are produced by bombardment under high vacuum using an electron beam

Correct Answer: Ionization occurs via gas-phase ion–molecule reactions initiated by a corona discharge at atmospheric pressure

Q2. Which analytes are typically best suited for APCI?

  • Moderately polar, thermally stable small-to-medium molecules (e.g., steroids, beta-blockers, lipids up to ~1,500 Da)
  • Highly polar peptides and intact proteins requiring multiple charging
  • Highly nonpolar PAHs best ionized with dopants
  • Thermally unstable oligonucleotides and labile glycans

Correct Answer: Moderately polar, thermally stable small-to-medium molecules (e.g., steroids, beta-blockers, lipids up to ~1,500 Da)

Q3. In positive-mode APCI, the dominant primary ionization step for many analytes is:

  • Proton transfer from H3O+(H2O)n solvent clusters to the analyte
  • Direct attachment of sodium ions generated at the corona needle
  • Electron capture by the analyte to form [M]•−
  • Photoionization of analyte π systems in the vapor phase

Correct Answer: Proton transfer from H3O+(H2O)n solvent clusters to the analyte

Q4. In negative-mode APCI, analyte ionization commonly proceeds by:

  • Electron capture/charge transfer from O2−(H2O)n and related reagent anions
  • Deprotonation exclusively by hydroxide ions formed from electrolysis
  • Formation of multiply charged anions by droplet fission
  • Resonance-enhanced multiphoton ionization of analytes

Correct Answer: Electron capture/charge transfer from O2−(H2O)n and related reagent anions

Q5. Increasing corona needle voltage/current in APCI typically results in:

  • Higher reagent-ion density, which can increase ionization efficiency but may also elevate in-source oxidation/fragmentation
  • Lower reagent-ion density and reduced sensitivity
  • Elimination of chemical background ions
  • Replacement of proton transfer by electron impact ionization

Correct Answer: Higher reagent-ion density, which can increase ionization efficiency but may also elevate in-source oxidation/fragmentation

Q6. Best practice for setting the APCI vaporizer temperature is to:

  • High enough to fully vaporize droplets/solvent (typically 300–500°C) without thermally degrading analytes
  • As low as possible to minimize desolvation energy
  • Above 600°C to convert all molecules to radicals
  • Unimportant, because APCI occurs in the liquid phase

Correct Answer: High enough to fully vaporize droplets/solvent (typically 300–500°C) without thermally degrading analytes

Q7. Which LC flow-rate range is commonly well tolerated by APCI without splitting?

  • 0.2–1.0 mL/min (often without split) is well tolerated by APCI
  • Must be <0.05 mL/min to avoid flooding the source
  • Requires nanospray flow rates for best sensitivity
  • Only works with flow rates >2 mL/min

Correct Answer: 0.2–1.0 mL/min (often without split) is well tolerated by APCI

Q8. Which statement about mobile-phase additives and APCI is correct?

  • APCI is generally more tolerant of buffers/ion-pair reagents (e.g., TFA) than ESI, with less ion suppression
  • APCI is completely unaffected by any salts or ion-pairing agents
  • APCI requires strictly salt-free mobile phases for ionization to occur
  • APCI only works when ammonium formate is present

Correct Answer: APCI is generally more tolerant of buffers/ion-pair reagents (e.g., TFA) than ESI, with less ion suppression

Q9. APCI and APPI differ primarily because:

  • APCI uses a corona needle; APPI uses a UV lamp and often a dopant
  • Both APCI and APPI require UV-active dopants
  • APCI is preferred over APPI for very nonpolar aromatics
  • APPI cannot operate at atmospheric pressure

Correct Answer: APCI uses a corona needle; APPI uses a UV lamp and often a dopant

Q10. Which component is NOT typical of an APCI source?

  • UV lamp for photon ionization of dopants
  • Heated nebulizer/vaporizer
  • Corona discharge needle/electrode
  • Curtain/sheath gas flow (usually nitrogen)

Correct Answer: UV lamp for photon ionization of dopants

Q11. The predominant positive-mode APCI ions for many drugs are:

  • [M+H]+ and sometimes [M+NH4]+, with minimal multiply charged ions
  • Predominantly [M+2H]2+ and [M+3H]3+ ions
  • [M−H]− as the main species
  • Radical cations [M]+• as the dominant ions

Correct Answer: [M+H]+ and sometimes [M+NH4]+, with minimal multiply charged ions

Q12. Adding ammonium acetate in positive-mode APCI often promotes:

  • Formation of [M+NH4]+ adducts that can enhance sensitivity
  • Exclusive formation of [M+Na]+ ions
  • Suppression of all analyte signals due to cluster ion formation only
  • Conversion to radical cations [M]+•

Correct Answer: Formation of [M+NH4]+ adducts that can enhance sensitivity

Q13. Which analyte is most likely to show improved response with APCI vs ESI at 1 mL/min and 0.1% TFA?

  • Hydrophobic corticosteroids
  • Highly polar phosphopeptides
  • Intact monoclonal antibodies
  • Oligonucleotides (20-mer)

Correct Answer: Hydrophobic corticosteroids

Q14. To mitigate matrix-induced ion suppression in APCI, a practical strategy is to:

  • Optimize curtain/nebulizer gas and vaporizer temperature to improve desolvation and adjust sampling/cone voltage
  • Lower corona current to zero
  • Replace nitrogen with oxygen as the nebulizing gas
  • Add excess sodium chloride to outcompete matrix ions

Correct Answer: Optimize curtain/nebulizer gas and vaporizer temperature to improve desolvation and adjust sampling/cone voltage

Q15. Compared to ESI, APCI tends to:

  • Slightly higher propensity for in-source fragmentation of fragile analytes due to higher thermal/energetic environment
  • Always lower in-source fragmentation and completely soft ionization
  • Formation of extensive multiply charged fragments
  • No capability to fragment ions by varying potentials

Correct Answer: Slightly higher propensity for in-source fragmentation of fragile analytes due to higher thermal/energetic environment

Q16. Regarding polarity switching for quantitation in APCI-LC–MS:

  • It is feasible with fast switching times, enabling positive/negative analytes in a single run on modern instruments
  • It is not possible; separate runs are mandatory
  • Switching requires venting the source to atmosphere
  • It only works if APPI mode is also enabled

Correct Answer: It is feasible with fast switching times, enabling positive/negative analytes in a single run on modern instruments

Q17. Analytes analyzed by APCI should be thermally stable primarily because:

  • Because they must survive vaporization in the heated nebulizer prior to gas-phase ionization
  • Because they are ionized by a UV lamp that heats the molecules
  • Because APCI uses vacuum ovens to bake the LC effluent
  • Because they must be sublimed onto a MALDI plate

Correct Answer: Because they must survive vaporization in the heated nebulizer prior to gas-phase ionization

Q18. Common positive-mode reagent/background ions in APCI include:

  • H3O+ and solvent cluster ions such as H3O+(H2O)n
  • Cs+ generated from the corona needle
  • NO2+ formed exclusively from air and dominating spectra
  • Electron beam–induced [M]•− of the analyte

Correct Answer: H3O+ and solvent cluster ions such as H3O+(H2O)n

Q19. In positive-mode APCI, formation of radical cations [M]+• by charge transfer is most favored for:

  • Molecules with high gas-phase ionization energies lower than that of the reagent ions (e.g., easily oxidizable aromatics)
  • All analytes irrespective of structure
  • Only inorganic salts
  • Large proteins with multiple basic sites

Correct Answer: Molecules with high gas-phase ionization energies lower than that of the reagent ions (e.g., easily oxidizable aromatics)

Q20. During APCI-LC–MS at 0.8 mL/min, a moderately polar drug shows low signal. Which adjustment is most likely to improve sensitivity?

  • Increase vaporizer temperature and/or curtain gas to achieve complete vaporization; ensure corona current within manufacturer’s recommended range
  • Switch to nanospray flow rates without changing source type
  • Add large amounts of non-volatile phosphate buffer
  • Disable the corona needle to reduce background

Correct Answer: Increase vaporizer temperature and/or curtain gas to achieve complete vaporization; ensure corona current within manufacturer’s recommended range

Leave a Comment