Types of impurities MCQs With Answer

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Introduction: Types of Impurities MCQs With Answer for B. Pharm

Types of impurities in pharmaceuticals include organic impurities (process-related impurities, intermediates, degradation products), inorganic impurities (reagents, catalysts, residual salts, elemental impurities), and residual solvents. B. Pharm students must know ICH guidelines (Q3A/Q3B for impurities in drug substances/products, Q3C for residual solvents, Q3D for elemental impurities), pharmacopeial standards (USP, IP, BP), and quality control tools like impurity profiling, limit tests, HPLC/GC/TLC, LC–MS, ICP–MS, and Karl Fischer. Understanding sources (raw materials, synthesis, packaging leachables, microbiological contamination), stability/forced degradation, specifications, thresholds, and risk assessment is vital for GMP-compliant manufacturing and safe medicines. This SEO-friendly set provides exam-focused practice on classification, identification, control, and analysis. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which statement best defines an impurity in a pharmaceutical substance?

  • Any component present in the drug substance that is not the desired active molecule
  • Any excipient intentionally added to the formulation
  • Only toxic substances introduced during manufacturing
  • Only degradation products formed during storage

Correct Answer: Any component present in the drug substance that is not the desired active molecule

Q2. The three primary categories of impurities as per pharmacopeial/ICH classification are:

  • Organic impurities, inorganic impurities, residual solvents
  • Physical, chemical, biological
  • Known, unknown, suspected
  • Toxic, non-toxic, inert

Correct Answer: Organic impurities, inorganic impurities, residual solvents

Q3. Process-related impurities are best described as:

  • By-products, unreacted starting materials, reagents, and catalysts from synthesis
  • Products formed due to long-term storage at high humidity
  • Contaminants entering from packaging during distribution
  • Microbial endotoxins arising in sterile manufacturing

Correct Answer: By-products, unreacted starting materials, reagents, and catalysts from synthesis

Q4. Degradation products are primarily generated due to:

  • Chemical change of the API under stress or storage conditions
  • Accidental mixing of raw materials
  • Residual solvents not removed during drying
  • Inadequate filtration of particulates

Correct Answer: Chemical change of the API under stress or storage conditions

Q5. Which ICH guideline addresses impurities in new drug substances (organic impurities)?

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

Correct Answer: ICH Q3A

Q6. Residual solvents are controlled according to which guideline?

  • ICH Q3C
  • ICH Q1A
  • ICH Q2
  • ICH Q10

Correct Answer: ICH Q3C

Q7. Elemental impurities (such as Pd, Pb, Cd) are addressed by:

  • ICH Q3D
  • ICH Q6A
  • ICH Q1B
  • ICH E6

Correct Answer: ICH Q3D

Q8. Class 1 residual solvents (ICH Q3C) are characterized as:

  • Solvents to be avoided due to unacceptable toxicity
  • Solvents with low toxic potential
  • Solvents with limited toxic potential
  • Solvents used only in parenteral formulations

Correct Answer: Solvents to be avoided due to unacceptable toxicity

Q9. Which is a Class 1 residual solvent?

  • Benzene
  • Ethanol
  • Acetone
  • Ethyl acetate

Correct Answer: Benzene

Q10. The most appropriate technique to quantify residual solvents in APIs is:

  • Gas chromatography (often with headspace)
  • UV–Visible spectrophotometry
  • Thin-layer chromatography
  • Potentiometric titration

Correct Answer: Gas chromatography (often with headspace)

Q11. The USP general chapter for Residual Solvents testing is:

  • USP <467>
  • USP <85>
  • USP <61>
  • USP <701>

Correct Answer: USP <467>

Q12. The outdated “Heavy Metals” colorimetric test (USP <231>) has been replaced by risk-based limits in:

  • USP <232> and <233>
  • USP <905> and <711>
  • USP <85> and <151>
  • USP <1231> and <1225>

Correct Answer: USP <232> and <233>

Q13. The preferred instrumental technique to quantify elemental impurities at trace levels is:

  • ICP–MS
  • HPLC–UV
  • Flame photometry
  • FT-IR

Correct Answer: ICP–MS

Q14. A simple and accurate method for water content in many drug substances is:

  • Karl Fischer titration
  • Loss on drying at 105°C
  • Gas chromatography
  • UV absorbance at 254 nm

Correct Answer: Karl Fischer titration

Q15. “Sulphated ash” primarily estimates:

  • Inorganic residue remaining after incineration with sulfuric acid
  • Organic volatile impurities
  • Moisture content in the sample
  • Loss of solvents from the matrix

Correct Answer: Inorganic residue remaining after incineration with sulfuric acid

Q16. Which statement best describes a stability-indicating method?

  • An analytical method that separates and quantifies API and all degradation products
  • A method validated only for precision
  • A method used exclusively for dissolution testing
  • A method that measures only API potency

Correct Answer: An analytical method that separates and quantifies API and all degradation products

Q17. Forced degradation studies are performed to:

  • Elucidate degradation pathways and develop stability-indicating methods
  • Increase API shelf-life artificially
  • Reduce the number of impurities formed
  • Meet packaging qualification requirements only

Correct Answer: Elucidate degradation pathways and develop stability-indicating methods

Q18. Which is commonly used for oxidative stress in forced degradation?

  • Hydrogen peroxide
  • Sodium chloride
  • Carbon dioxide
  • Ethanol

Correct Answer: Hydrogen peroxide

Q19. Which photostability guideline describes light stress testing?

  • ICH Q1B
  • ICH Q3B
  • ICH Q8
  • ICH Q9

Correct Answer: ICH Q1B

Q20. In HPLC method validation (ICH Q2), “specificity” refers to the ability to:

  • Measure accurately the analyte in presence of impurities and excipients
  • Reproduce results across analysts
  • Produce linear response with concentration
  • Detect small changes in analyte concentration

Correct Answer: Measure accurately the analyte in presence of impurities and excipients

Q21. For initial impurity screening in API synthesis, a rapid and economical technique is:

  • Thin-layer chromatography
  • Nuclear magnetic resonance
  • Differential scanning calorimetry
  • Polarimetry

Correct Answer: Thin-layer chromatography

Q22. For structural elucidation of unknown impurities separated by HPLC, the best detector/technique is:

  • LC–MS
  • Refractive index detector
  • Conductivity detector
  • Flame ionization detector

Correct Answer: LC–MS

Q23. Headspace sampling in GC is particularly useful for detecting:

  • Volatile residual solvents
  • Non-volatile inorganic salts
  • High-molecular-weight polymers
  • Protein impurities

Correct Answer: Volatile residual solvents

Q24. Leachables in pharmaceuticals originate from:

  • Packaging materials during storage
  • Residual water in the API
  • Excipients intentionally added
  • Analyst handling during testing

Correct Answer: Packaging materials during storage

Q25. Extractables are defined as:

  • Compounds that can be pulled from packaging under aggressive conditions
  • Compounds that always migrate into the drug product during storage
  • Compounds added as antioxidants to the formulation
  • Microbial metabolites produced in culture

Correct Answer: Compounds that can be pulled from packaging under aggressive conditions

Q26. Which is a common source of inorganic impurities?

  • Residual catalysts like palladium from hydrogenation
  • Photolysis of the API
  • Microbial contamination
  • Evaporation of ethanol

Correct Answer: Residual catalysts like palladium from hydrogenation

Q27. A typical example of a process solvent that may remain as a residual impurity is:

  • Dimethylformamide (DMF)
  • Sodium chloride
  • Magnesium stearate
  • Microcrystalline cellulose

Correct Answer: Dimethylformamide (DMF)

Q28. Microbiological impurities in non-sterile products are controlled by:

  • Total aerobic microbial count (TAMC) and total yeast and mold count (TYMC)
  • Optical rotation
  • Friability test
  • Viscosity measurement

Correct Answer: Total aerobic microbial count (TAMC) and total yeast and mold count (TYMC)

Q29. Bacterial endotoxins in parenterals are measured using:

  • LAL assay
  • HPLC–UV
  • GC–FID
  • DSC

Correct Answer: LAL assay

Q30. Nitrosamine impurities are of concern primarily because they are:

  • Genotoxic and potentially carcinogenic
  • Highly volatile but nontoxic
  • Inorganic salts that affect taste
  • Inert excipients

Correct Answer: Genotoxic and potentially carcinogenic

Q31. A commonly applied concept for acceptable daily intake of most genotoxic impurities is the TTC, approximately:

  • 1.5 µg/day
  • 15 µg/day
  • 0.15 µg/day
  • 150 µg/day

Correct Answer: 1.5 µg/day

Q32. In a product specification, impurity limits are expressed as:

  • Acceptance criteria for individual and total impurities
  • Batch manufacturing records
  • Cleaning validation limits
  • Supplier qualification requirements

Correct Answer: Acceptance criteria for individual and total impurities

Q33. The “reporting threshold” for impurities means the level at which:

  • An impurity must be reported in the documentation
  • An impurity must be removed completely
  • A toxicology study becomes mandatory
  • Regulatory approval is automatically withdrawn

Correct Answer: An impurity must be reported in the documentation

Q34. The “identification threshold” indicates the level at which:

  • The structure of the impurity should be identified where feasible
  • The impurity may be ignored
  • No analytical method is required
  • Only visual inspection is needed

Correct Answer: The structure of the impurity should be identified where feasible

Q35. The “qualification threshold” refers to the level at which:

  • Safety data may be required to establish acceptability
  • Analytical method validation is unnecessary
  • Batch must be rejected automatically
  • Only organoleptic testing is performed

Correct Answer: Safety data may be required to establish acceptability

Q36. Peak purity assessment in HPLC helps to:

  • Ensure a chromatographic peak is not composed of co-eluting impurities
  • Measure the melting point of the analyte
  • Determine the partition coefficient
  • Quantify elemental impurities

Correct Answer: Ensure a chromatographic peak is not composed of co-eluting impurities

Q37. To resolve co-elution of an impurity with API in HPLC, the first strategy is to:

  • Modify mobile phase composition or column selectivity
  • Increase injection volume
  • Raise column temperature indefinitely
  • Switch to UV–Vis spectroscopy

Correct Answer: Modify mobile phase composition or column selectivity

Q38. Chiral impurities (undesired enantiomer) are best analyzed using:

  • Chiral HPLC columns
  • Flame photometry
  • Potentiometric titration
  • Thin-layer chromatography with silica gel GF

Correct Answer: Chiral HPLC columns

Q39. Which of the following is a Class 3 residual solvent (low toxic potential)?

  • Ethanol
  • Benzene
  • 1,2-Dichloroethane
  • Carbon tetrachloride

Correct Answer: Ethanol

Q40. Which factor most increases hydrolytic degradation impurities?

  • High moisture content and unsuitable pH
  • Low temperature storage
  • Amber light-protective packaging
  • Use of dry nitrogen headspace

Correct Answer: High moisture content and unsuitable pH

Q41. Limit tests for anions like chloride and sulfate in IP/USP are generally based on:

  • Precipitation and turbidity comparison
  • Fluorescence intensity
  • Potentiometric titration only
  • Conductivity exclusively

Correct Answer: Precipitation and turbidity comparison

Q42. The classical limit test for iron in pharmacopeias uses formation of:

  • A colored complex compared against a standard
  • A volatile ester
  • A crystalline polymorph
  • An electrochemical deposit

Correct Answer: A colored complex compared against a standard

Q43. The historical Gutzeit method is associated with testing of:

  • Arsenic
  • Chloride
  • Peroxide
  • Lead

Correct Answer: Arsenic

Q44. A formulation risk to impurity formation from packaging is best mitigated by:

  • Extractables and leachables studies with suitable packaging selection
  • Increasing fill volume in the same container
  • Adding more colorants
  • Using higher compression force in tablets

Correct Answer: Extractables and leachables studies with suitable packaging selection

Q45. ICH Q6A primarily addresses:

  • Specifications: test procedures and acceptance criteria
  • Photostability testing
  • Residual solvents limits
  • Validation of analytical procedures

Correct Answer: Specifications: test procedures and acceptance criteria

Q46. A robust control strategy for impurities includes all EXCEPT:

  • Ignoring unknown impurities below any level
  • Setting specification limits
  • Using stability-indicating methods
  • Supplier and raw material controls

Correct Answer: Ignoring unknown impurities below any level

Q47. In HPLC impurity profiling, a gradient elution is often preferred because it:

  • Improves separation of components with wide polarity range
  • Always shortens run time regardless of method
  • Eliminates need for column conditioning
  • Removes the requirement for system suitability

Correct Answer: Improves separation of components with wide polarity range

Q48. Which change most likely reduces oxidative impurities in a formulation?

  • Use of antioxidants and oxygen-impermeable packaging
  • Increasing tablet hardness only
  • Adding flavors and colors
  • Raising storage temperature

Correct Answer: Use of antioxidants and oxygen-impermeable packaging

Q49. The peroxide value test in oils indicates:

  • Extent of oxidative rancidity (peroxide impurities)
  • Amount of saturated fatty acids
  • Level of residual solvents
  • Presence of heavy metals

Correct Answer: Extent of oxidative rancidity (peroxide impurities)

Q50. Good Manufacturing Practices (GMP) help control impurities primarily by:

  • Preventing contamination and ensuring consistent, validated processes
  • Eliminating the need for quality control testing
  • Allowing flexible undocumented process changes
  • Focusing only on finished product testing

Correct Answer: Preventing contamination and ensuring consistent, validated processes

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