Impurities in APIs: types, sources and genotoxic impurity considerations MCQs With Answer

Introduction: This quiz collection on “Impurities in APIs: types, sources and genotoxic impurity considerations” is tailored for M.Pharm students studying Pharmaceutical Process Chemistry (MPC 204T). It emphasizes the practical and regulatory aspects of impurity classification, identification, control and risk assessment with a focus on genotoxic impurities. Questions span organic, inorganic and residual solvent impurities, synthetic and degradation sources, analytical detection techniques and regulatory frameworks such as ICH Q3A/Q3B and ICH M7. These multiple-choice questions are designed to test conceptual understanding, application of control strategies and interpretation of limits used in real-world API development and quality control. Use them for exam prep and classroom revision.

Q1. Which category best describes impurities that arise from the synthetic route, such as unreacted starting materials and by‑products?

• Degradation products
• Process-related organic impurities
• Residual solvents
• Inorganic contaminants

Correct Answer: Process-related organic impurities

Q2. According to ICH M7, what is the commonly applied threshold of toxicological concern (TTC) for controlling unexpected genotoxic impurities when no compound-specific toxicity data exist?

• 1.5 micrograms per day
• 15 micrograms per day
• 150 micrograms per day
• 0.15 micrograms per day

Correct Answer: 1.5 micrograms per day

Q3. Which analytical technique is most appropriate for sensitive quantitation of trace genotoxic organic impurities in an API matrix?

• UV spectrophotometry
• High-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS)
• Titration
• Polarimetry

Correct Answer: High-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS)

Q4. What type of impurity is formed in an API due to hydrolysis, oxidation or photolysis during storage?

• Process-related impurity
• Degradation product
• Residual catalyst
• Extractable/leachable

Correct Answer: Degradation product

Q5. Which regulatory guideline specifically addresses impurities in new drug substances and products, including thresholds for reporting, identification and qualification?

• ICH Q8
• ICH Q3A/Q3B
• ICH Q9
• ICH S4

Correct Answer: ICH Q3A/Q3B

Q6. A reagent used in synthesis leaves a ppm-level trace in the API. Under which impurity class would this most likely be categorized?

• Residual solvents
• Process-related organic impurities
• Inorganic impurities
• Polymorphic forms

Correct Answer: Process-related organic impurities

Q7. Which source is the most likely origin of metal impurities in an API?

• Oxidative degradation
• Reaction catalysts and equipment contact
• Residual API enantiomer
• Packaging extractables

Correct Answer: Reaction catalysts and equipment contact

Q8. When conducting a risk assessment for potential mutagenic impurities, which in silico tool is commonly used to predict DNA reactivity?

• Ames test
• QSAR and structural alerts
• HPLC retention modeling
• Thermal gravimetric analysis

Correct Answer: QSAR and structural alerts

Q9. For an impurity with structural alerts for mutagenicity but without experimental data, the recommended approach under ICH M7 typically begins with:

• Clinical trials to assess patient outcomes
• Applying the TTC with analytical control, and performing additional testing if necessary
• Ignoring the impurity if below 1% w/w
• Immediate product recall

Correct Answer: Applying the TTC with analytical control, and performing additional testing if necessary

Q10. Which of the following is NOT a common strategy to lower impurity levels during API manufacture?

• Route selection to avoid formation of the impurity
• Optimized purification and crystallization steps
• Prolonged storage to allow impurity degradation
• Use of scavengers to remove residual reagents or catalysts

Correct Answer: Prolonged storage to allow impurity degradation

Q11. What is the primary reason residual solvents are controlled in APIs?

• They always form new degradation products
• They can be toxic or affect product quality and patient safety
• They improve solubility of the API
• They increase shelf life

Correct Answer: They can be toxic or affect product quality and patient safety

Q12. Which impurity limit concept defines the maximum level of an impurity at which additional toxicological qualification is not required because exposure is considered negligible?

• Identification threshold
• Qualification threshold
• Reporting threshold
• Threshold of Toxicological Concern (TTC)

Correct Answer: Threshold of Toxicological Concern (TTC)

Q13. In the context of genotoxic impurities, what does the term “potency” refer to?

• The solubility of the impurity in water
• The relative strength of the impurity to cause genetic damage per unit dose
• The volatility of the impurity
• The melting point of the impurity

Correct Answer: The relative strength of the impurity to cause genetic damage per unit dose

Q14. Which experimental assay is commonly used as a first-line in vitro test for mutagenic potential of an impurity?

• Chromatographic fingerprinting
• Ames (bacterial reverse mutation) test
• IR spectroscopy
• DSC (differential scanning calorimetry)

Correct Answer: Ames (bacterial reverse mutation) test

Q15. What is the importance of establishing an identification threshold for impurities in drug substances?

• It determines the color of the final product
• It defines at what level an impurity must be structurally identified during development
• It sets the price of raw materials
• It regulates the manufacturing temperature

Correct Answer: It defines at what level an impurity must be structurally identified during development

Q16. Which control measure is most effective to prevent introduction of extractables and leachables as impurities?

• Using high‑pressure reactors
• Careful selection and qualification of packaging and contact materials
• Increasing reaction temperature
• Adding more solvent

Correct Answer: Careful selection and qualification of packaging and contact materials

Q17. When calculating a permissible concentration limit for a genotoxic impurity in an API, which two factors are essential?

• Melting point and boiling point of the impurity
• Acceptable daily intake (e.g., TTC) and the maximum daily dose of the API
• Color and odor of the impurity
• Molecular weight and refractive index

Correct Answer: Acceptable daily intake (e.g., TTC) and the maximum daily dose of the API

Q18. Why are inorganic impurities such as heavy metals controlled in APIs?

• They can act as catalysts to speed up dissolution
• They may be toxic, cause adverse reactions or affect stability and assay results
• They always react to form new APIs
• They increase the potency of the drug

Correct Answer: They may be toxic, cause adverse reactions or affect stability and assay results

Q19. Which practice helps demonstrate that a genotoxic impurity will not be generated during routine storage of the finished product?

• Conducting forced degradation and stability studies to identify potential degradants
• Measuring only initial purity after synthesis
• Relying solely on supplier certificates for starting materials
• Assuming refrigeration will eliminate all risks

Correct Answer: Conducting forced degradation and stability studies to identify potential degradants

Q20. In a control strategy, what is the role of acceptance criteria in the specifications for impurity limits?

• They specify the color and texture of the API
• They define allowable impurity levels to ensure safety, efficacy and regulatory compliance
• They determine the supplier’s profit margin
• They mandate the marketing claims for the product

Correct Answer: They define allowable impurity levels to ensure safety, efficacy and regulatory compliance

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