Sources of impurities MCQs With Answer

Sources of Impurities MCQs With Answer for B. Pharm: B. Pharm students must master the sources of pharmaceutical impurities to ensure drug quality control, safety, and regulatory compliance. This concise, SEO-friendly guide covers impurities from raw materials, starting materials, reagents, residual solvents, catalysts, water systems, equipment, packaging/closures, degradation products (hydrolysis, oxidation, photolysis), microbial/endotoxin contamination, and extractables/leachables. It aligns with ICH Q3A/Q3B/Q3C/Q3D, ICH M7, and GMP expectations for APIs and drug products. Learn how manufacturing processes, storage, excipients, and environment create organic, inorganic, and residual solvent impurities, and how to prevent them via risk assessment, validated water/solvent controls, and appropriate packaging. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which is a common source of elemental impurities like Pd, Pt, or Ni in synthetic APIs?

• Residual catalysts from synthetic steps
• Photodegradation during storage
• Incomplete blending of excipients
• Primary packaging headspace gas

Correct Answer: Residual catalysts from synthetic steps

Q2. A likely source of chloride impurity in an API batch is:

• Use of hydrochloric acid or chloride-containing reagents
• Use of nitrogen for inerting
• Packaging with amber glass
• Compression force during tableting

Correct Answer: Use of hydrochloric acid or chloride-containing reagents

Q3. Residual solvent impurities most often arise from:

• Incomplete drying after solvent-based processing
• Excessive sieving of granules
• Use of desiccants in packaging
• High compression speed

Correct Answer: Incomplete drying after solvent-based processing

Q4. Which water-related source most commonly contributes to microbial impurities in non-sterile products?

• Biofilm formation in the purified water system
• Use of nitrogen blanketing
• High-shear granulation
• Laminar airflow cabinets

Correct Answer: Biofilm formation in the purified water system

Q5. Nitrosamine impurities can originate from:

• Reaction of secondary amines with nitrites during acidic workup
• Hydrolysis of esters in neutral water
• Adsorption of API on filters
• Use of stainless steel 316L

Correct Answer: Reaction of secondary amines with nitrites during acidic workup

Q6. Leachables are most often introduced into drug products from:

• Container–closure systems and packaging materials
• Excess vacuum in dryers
• Inert gas sparging
• Salt formation during crystallization

Correct Answer: Container–closure systems and packaging materials

Q7. Elemental impurities like Fe, Cr, and Ni may increase due to:

• Equipment wear and corrosion
• High humidity during storage
• Exposure to fluorescent light
• Incorrect labeling

Correct Answer: Equipment wear and corrosion

Q8. A frequent source of sulfate impurity in a product is:

• Use of sulfuric acid or sulfate-containing excipients
• CO2 ingression from air
• Magnesium stearate lubrication
• Use of nitrogen headspace

Correct Answer: Use of sulfuric acid or sulfate-containing excipients

Q9. Peroxide impurities often come from:

• Oxidized solvents/excipients like ethers or PEGs
• Glass vials
• Stainless steel passivation
• Tablet tooling polishing

Correct Answer: Oxidized solvents/excipients like ethers or PEGs

Q10. Which is a typical source of endotoxin contamination in parenterals?

• Gram-negative bacteria in water for injection systems
• Use of titanium dioxide in film coating
• Use of dry heat depyrogenation
• Vacuum oven drying

Correct Answer: Gram-negative bacteria in water for injection systems

Q11. An impurity increasing only under UV exposure most likely originates from:

• Photodegradation due to inadequate light-protective packaging
• Over-lubrication with magnesium stearate
• Insufficient granulation time
• Incorrect pH adjustment

Correct Answer: Photodegradation due to inadequate light-protective packaging

Q12. Which practice is a common source of cross-contamination impurities?

• Inadequate cleaning of shared manufacturing equipment
• Use of dedicated utilities
• Closed transfer systems
• Use of single-use liners

Correct Answer: Inadequate cleaning of shared manufacturing equipment

Q13. Increased sodium and silica in solution products can arise from:

• Alkali leaching from glass containers
• Use of PTFE gaskets
• Granulation with purified water
• Room-temperature storage

Correct Answer: Alkali leaching from glass containers

Q14. A new oxidative impurity appears when switching to recycled solvent. The likely source is:

• Carryover contaminants in inadequately controlled recovered solvent
• Higher compression force
• Use of lactose monohydrate
• Switch to blister packaging

Correct Answer: Carryover contaminants in inadequately controlled recovered solvent

Q15. Residual amine starting material in the final API is an impurity sourced from:

• Incomplete reaction or inadequate purification of intermediates
• Photolysis in warehouse
• Filter clogging
• Label ink migration

Correct Answer: Incomplete reaction or inadequate purification of intermediates

Q16. Class 1 residual solvents (ICH Q3C) like benzene may originate from:

• Contaminated commercial-grade solvents used in processing
• Desiccant overuse
• Use of stainless steel mixers
• Exposure to nitrogen

Correct Answer: Contaminated commercial-grade solvents used in processing

Q17. A likely source of metal particles in milled API is:

• Mechanical abrasion from mills and screens
• Use of HEPA filters
• Gelatin capsule shells
• Cold room storage

Correct Answer: Mechanical abrasion from mills and screens

Q18. Which excipient-related source can promote Maillard reaction impurities with amine APIs?

• Reducing sugars present in lactose or dextrose
• Microcrystalline cellulose
• Povidone K30 alone
• Sodium starch glycolate

Correct Answer: Reducing sugars present in lactose or dextrose

Q19. A source of hydrolytic degradation impurities is most often:

• High moisture or elevated humidity exposure
• Inert nitrogen headspace
• Low-temperature storage
• Amber glass use

Correct Answer: High moisture or elevated humidity exposure

Q20. Which is a typical source of extractables that become leachables in solution products?

• Plasticizers and antioxidants from elastomeric stoppers
• Stainless steel passivation layer
• Silica gel desiccant
• Glassine paper labels

Correct Answer: Plasticizers and antioxidants from elastomeric stoppers

Q21. Elemental impurities risk assessment per ICH Q3D largely targets sources from:

• Catalysts, reagents, water, equipment, and excipients
• Tablet press speed
• Warehouse lighting
• Batch numbering practices

Correct Answer: Catalysts, reagents, water, equipment, and excipients

Q22. Unknown peaks appearing only after peroxide stress in stability studies likely originate from:

• Oxidative degradation susceptibility of the API
• Photolysis of colorants
• Residual moisture
• Salt disproportionation

Correct Answer: Oxidative degradation susceptibility of the API

Q23. Endotoxin contamination is most likely introduced by:

• Use of non-depyrogenated equipment and WFI contact surfaces
• Use of nitrogen purging
• Cold chain logistics
• Gamma-irradiated stoppers

Correct Answer: Use of non-depyrogenated equipment and WFI contact surfaces

Q24. Which is a common source of carbonate impurities in alkaline aqueous formulations?

• Absorption of CO2 from ambient air
• Migration from PVC blisters
• Leaching from amber glass
• Magnesium stearate hydrolysis

Correct Answer: Absorption of CO2 from ambient air

Q25. A stereochemical impurity (wrong enantiomer) often originates from:

• Non-selective chiral synthesis or incomplete chiral resolution
• Photodegradation during shipping
• Humidity fluctuations in warehouse
• Tablet film coating defects

Correct Answer: Non-selective chiral synthesis or incomplete chiral resolution

Q26. Increased sulfate ash in excipients indicates inorganic impurities sourced from:

• Mineral residues, counterions, or processing aids
• Light exposure
• Low temperature storage
• Nitrogen blanketing

Correct Answer: Mineral residues, counterions, or processing aids

Q27. Aqueous peroxide in PEG-containing creams most likely forms due to:

• Auto-oxidation of polyethylene glycol under air and light
• Interaction with aluminum tubes
• Hydrolysis of parabens
• Adsorption on fillers

Correct Answer: Auto-oxidation of polyethylene glycol under air and light

Q28. Particulate contamination from filters can arise from:

• Fiber shedding or extractables from non-compatible filter media
• Use of 0.2 μm sterilizing filters
• Nitrogen sparging
• Cold room storage

Correct Answer: Fiber shedding or extractables from non-compatible filter media

Q29. Which source commonly leads to residual solvent entrapment in granules?

• Inadequate drying or dense granule formation
• Use of fluid bed processing
• Low inlet air temperature control
• Use of non-ionic surfactants

Correct Answer: Inadequate drying or dense granule formation

Q30. An increase in unknown impurity after switching to HDPE bottles suggests a source from:

• Leachables such as antioxidants (e.g., BHT) from plastic
• Oxidation by stainless steel
• CO2 absorption by product
• Excess milling time

Correct Answer: Leachables such as antioxidants (e.g., BHT) from plastic

Q31. Dimethylamine in materials may originate from:

• Thermal decomposition of DMF solvent
• Glass delamination
• Use of nitrogen headspace
• Photolysis of dyes

Correct Answer: Thermal decomposition of DMF solvent

Q32. Which condition most promotes hydrolysis-derived impurities in esters and lactams?

• High moisture and extreme pH
• Low oxygen levels
• Amber light exposure
• Dry nitrogen atmosphere

Correct Answer: High moisture and extreme pH

Q33. Unknown peaks that correlate with high peroxide value in excipients are sourced from:

• Oxidized excipients initiating API degradation
• Dust in compression room
• Label adhesive migration
• High tablet hardness

Correct Answer: Oxidized excipients initiating API degradation

Q34. Which is a likely source of nitrite that can form nitrosamines?

• Contaminated salts or quench reagents containing nitrite
• Compressed air drying
• Silica gel desiccant
• Amber glass bottles

Correct Answer: Contaminated salts or quench reagents containing nitrite

Q35. Residual acids/bases used for pH adjustment can lead to impurities by:

• Forming counterions/salts or catalyzing degradation
• Cooling the reaction mass
• Improving solubility alone
• Reducing microbial load

Correct Answer: Forming counterions/salts or catalyzing degradation

Q36. Which packaging change increases risk of photolytic impurities?

• Switch from amber to clear glass
• Switch from HDPE to PP
• Use of foil–foil blisters
• Use of aluminum tubes

Correct Answer: Switch from amber to clear glass

Q37. An API that becomes amorphous after milling shows faster impurity formation because:

• Amorphous regions have higher molecular mobility and reactivity
• It excludes oxygen
• It reduces water sorption
• It improves crystal packing

Correct Answer: Amorphous regions have higher molecular mobility and reactivity

Q38. Which is a typical source of halogen impurities (e.g., bromide) in APIs?

• Use of hydrobromic acid or brominated reagents
• Use of nitrogen inerting
• Use of silica gel column
• Steam sterilization

Correct Answer: Use of hydrobromic acid or brominated reagents

Q39. A dimer impurity appearing upon air exposure is most consistent with:

• Oxidative coupling due to dissolved oxygen or peroxides
• Hydrolytic cleavage
• Photochemical N→O acyl shift
• Salt formation with HCl

Correct Answer: Oxidative coupling due to dissolved oxygen or peroxides

Q40. Which cleaning-related source commonly leaves residues in equipment?

• Inadequate rinse of alkaline detergents
• HEPA-filtered air
• Use of WFI
• Steam-in-place with condensate drain

Correct Answer: Inadequate rinse of alkaline detergents

Q41. Increased aluminum in solution products can originate from:

• Aluminum tubes or components in contact with product
• PTFE seals
• Amber Type I glass
• SS 316L tanks

Correct Answer: Aluminum tubes or components in contact with product

Q42. Class 2 solvent impurity toluene most likely remains due to:

• Use in crystallization with insufficient drying
• Migration from labels
• Leaching from rubber stoppers
• Hydrolysis of excipients

Correct Answer: Use in crystallization with insufficient drying

Q43. Which is a source of unknown impurities when switching to a different grade of an excipient?

• Trace impurities and processing aids unique to the new supplier
• Temperature mapping of warehouse
• Nitrogen inerting
• Photostable primary pack

Correct Answer: Trace impurities and processing aids unique to the new supplier

Q44. Glass delamination in parenteral vials primarily introduces:

• Silicate flakes and increased alkali in solution
• Peroxides
• Nitrosamines
• Polyaromatic hydrocarbons

Correct Answer: Silicate flakes and increased alkali in solution

Q45. A typical source of iron contamination during wet granulation is:

• Corroded stainless steel or carbon steel contact parts
• Amber glass bottles
• PTFE gaskets
• HDPE scoops

Correct Answer: Corroded stainless steel or carbon steel contact parts

Q46. Formation of solvates (e.g., ethanol solvate) as impurities originates from:

• Crystallization in presence of specific solvents
• Exposure to carbon dioxide
• Use of nitrogen purging
• Dry heat sterilization

Correct Answer: Crystallization in presence of specific solvents

Q47. Which water quality issue most contributes to inorganic impurities?

• High conductivity due to ionic contaminants
• Low temperature of water
• High dissolved oxygen
• Use of ozone for sanitization

Correct Answer: High conductivity due to ionic contaminants

Q48. A likely source of organic leachables in prefilled syringes is:

• Silicone oil used for plunger lubrication
• Stainless steel needles
• CO2 headspace
• Glass barrel siliconization by heat only

Correct Answer: Silicone oil used for plunger lubrication

Q49. Mutagenic impurities controlled under ICH M7 can arise from:

• Reagents, by-products, or nitrosation pathways in the synthesis
• Warehouse dust
• CO2 ingress
• Amber bottle storage

Correct Answer: Reagents, by-products, or nitrosation pathways in the synthesis

Q50. An impurity that increases during wet granulation drying at high temperature likely originates from:

• Thermal degradation accelerated by elevated drying temperatures
• Leaching from HDPE containers
• Nitrogen inerting
• Improved crystallinity

Correct Answer: Thermal degradation accelerated by elevated drying temperatures

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com