Purity and impurity profiling of drug substances MCQs With Answer

Introduction:

This blog presents a focused set of multiple-choice questions (MCQs) on purity and impurity profiling of drug substances tailored for M.Pharm students studying Product Development and Technology Transfer. The quiz covers regulatory guidelines, types and sources of impurities, analytical techniques for detection and identification, forced-degradation and stability-indicating methods, qualification/qualification concepts, and risk- and safety-based control strategies including genotoxic and elemental impurities. Questions are designed to deepen conceptual understanding and to reinforce practical knowledge required during drug substance development, specification setting and technology transfer. Use these MCQs for revision, self-assessment, or classroom discussion to strengthen mastery of impurity-related challenges in pharmaceutical development.

Q1. What best defines an impurity in a drug substance?

• A component present at therapeutic concentration that enhances drug efficacy
• An unintended chemical entity present in the drug substance that is not the desired active pharmaceutical ingredient
• A degradation product intentionally added to improve stability
• A standard reference compound used for assay calibration

Correct Answer: An unintended chemical entity present in the drug substance that is not the desired active pharmaceutical ingredient

Q2. Which of the following lists correctly represents the main categories of impurities encountered in drug substances?

• Organic impurities, inorganic impurities, and residual solvents
• Only degradation products and colorants
• Microbial contaminants, packaging materials, and enzymes
• Preservatives, flavours, and dyes

Correct Answer: Organic impurities, inorganic impurities, and residual solvents

Q3. Which ICH guideline specifically addresses impurities in new drug substances?

• ICH Q3A(R2)
• ICH Q3C
• ICH Q5C
• ICH Q9

Correct Answer: ICH Q3A(R2)

Q4. The ICH guideline that provides guidance on assessment and control of DNA reactive (mutagenic) impurities is:

• ICH Q3D
• ICH M7
• ICH Q1A
• ICH Q2(R1)

Correct Answer: ICH M7

Q5. Which ICH guideline is focused on elemental impurities (metals) and their permitted limits?

• ICH Q3B
• ICH Q3C
• ICH Q3D
• ICH Q5E

Correct Answer: ICH Q3D

Q6. Which analytical technique is most appropriate for routine quantitation of volatile residual solvents in a drug substance?

• High-performance liquid chromatography with UV detection (HPLC-UV)
• Headspace gas chromatography (HS-GC)
• Infrared spectroscopy (IR)
• Nuclear magnetic resonance (NMR)

Correct Answer: Headspace gas chromatography (HS-GC)

Q7. A stability‑indicating method is best defined as:

• A method that only measures the assay of the active without separating degradants
• A method capable of distinguishing and quantifying the active substance in presence of its degradation products, impurities and excipients
• A non-specific colorimetric test for product identity
• A microbial limit test used during stability studies

Correct Answer: A method capable of distinguishing and quantifying the active substance in presence of its degradation products, impurities and excipients

Q8. In forced degradation studies, achieving mass balance means:

• The sum of measured assay and degradation products approximates the initial amount of active substance
• Only the parent drug is detected and no degradants are formed
• All impurities are below the reporting threshold
• The chromatographic peak shape is symmetrical

Correct Answer: The sum of measured assay and degradation products approximates the initial amount of active substance

Q9. What is the primary objective of impurity qualification during drug substance development?

• To determine manufacturing cost impacts of impurities
• To establish analytical calibration curves for the impurity
• To ensure the toxicological safety of an impurity above certain levels and to support regulatory justification and control strategies
• To improve the drug’s pharmacokinetic profile

Correct Answer: To ensure the toxicological safety of an impurity above certain levels and to support regulatory justification and control strategies

Q10. A genotoxic impurity is best described as:

• An impurity that alters pharmacokinetics but is non‑mutagenic
• An impurity that causes direct or indirect damage to DNA leading to mutations
• A trace metal that accumulates in organs
• A solvent residue above acceptable limit

Correct Answer: An impurity that causes direct or indirect damage to DNA leading to mutations

Q11. In elemental impurity control, the acronym PDE stands for:

• Potential Daily Excipient
• Permitted Daily Exposure
• Primary Drug Element
• Permissible Dose Equivalence

Correct Answer: Permitted Daily Exposure

Q12. Which analytical technique provides the most powerful structural information for elucidating an unknown organic impurity?

• Ultraviolet-visible spectroscopy (UV-Vis)
• Mass spectrometry (MS) combined with tandem techniques and NMR spectroscopy
• Turbidity measurement
• Refractive index detection (RID)

Correct Answer: Mass spectrometry (MS) combined with tandem techniques and NMR spectroscopy

Q13. Forced degradation studies are performed primarily to:

• Estimate shelf-life solely from accelerated temperature data
• Generate known degradants to help develop and validate stability‑indicating analytical methods and understand degradation pathways
• Determine solubility limits
• Reduce production costs

Correct Answer: Generate known degradants to help develop and validate stability‑indicating analytical methods and understand degradation pathways

Q14. The ICH guideline that provides recommendations for residual solvent limits is:

• ICH Q3A
• ICH Q3C
• ICH Q3B
• ICH Q3D

Correct Answer: ICH Q3C

Q15. How does a limit test differ from a quantitative assay in impurity control?

• A limit test provides a pass/fail result against a defined acceptance level while a quantitative assay measures the actual amount of impurity
• A limit test is always more accurate than a quantitative assay
• A limit test identifies structure while a quantitative assay does not
• There is no difference; both terms are interchangeable

Correct Answer: A limit test provides a pass/fail result against a defined acceptance level while a quantitative assay measures the actual amount of impurity

Q16. Which of the following is NOT a typical source of impurities in a drug substance?

• Starting materials and reagents used in synthesis
• Degradation during storage or processing
• Intentional addition of stabilizing excipients into the drug substance bulk
• Residual solvents and catalysts from manufacturing

Correct Answer: Intentional addition of stabilizing excipients into the drug substance bulk

Q17. Which analytical technique is most suitable for trace determination of elemental impurities (metals) in a drug substance?

• Atomic absorption spectroscopy (AAS) with flame only
• Inductively coupled plasma mass spectrometry (ICP-MS)
• Thin-layer chromatography (TLC)
• Gas chromatography with flame ionization detection (GC-FID)

Correct Answer: Inductively coupled plasma mass spectrometry (ICP-MS)

Q18. The Threshold of Toxicological Concern (TTC) commonly applied for genotoxic impurities in ICH M7 is approximately:

• 1500 micrograms per day
• 1.5 micrograms per day
• 15 milligrams per day
• 0.001 micrograms per day

Correct Answer: 1.5 micrograms per day

Q19. Which process development control strategy is most effective to minimize formation of downstream impurities?

• Elimination or modification of impurity‑forming synthetic steps and inclusion of targeted purification steps such as recrystallization or chromatography
• Reducing analytical testing frequency
• Avoiding process validation
• Adding more packaging layers

Correct Answer: Elimination or modification of impurity‑forming synthetic steps and inclusion of targeted purification steps such as recrystallization or chromatography

Q20. For analysis of non‑volatile, polar impurity molecules that co-elute from LC, which MS ionization technique is typically preferred?

• Electron impact ionization (EI)
• Electrospray ionization (ESI)
• Gas-phase chemical ionization (CI)
• Cold field ionization (CFI)

Correct Answer: Electrospray ionization (ESI)

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