Chemical degradation of antibiotics is a vital subject for B.Pharm students, exploring how drugs lose potency through hydrolysis, oxidation, photodegradation, epimerization and racemization. This introduction emphasizes degradation kinetics, forced-degradation studies, stability-indicating assays, and ICH guidelines to predict shelf-life and identify toxic impurities. Key topics include pH-dependent hydrolysis, catalytic effects of metal ions and excipients, Arrhenius-based temperature acceleration, analytical tools (HPLC, LC–MS) for impurity profiling, and formulation strategies such as pH optimization, antioxidants, chelators, lyophilization and protective packaging. A deeper understanding enables rational formulation design and robust quality control of antibiotic products. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which mechanism is most associated with instability of beta-lactam antibiotics?
- Hydrolysis of the beta-lactam ring
- Oxidative cleavage of aromatic rings
- Photodimerization of side chains
- Racemization at an adjacent stereocenter
Correct Answer: Hydrolysis of the beta-lactam ring
Q2. Tetracycline antibiotics are particularly vulnerable to which chemical change?
- Epimerization at the C-4 center
- Nucleophilic aromatic substitution
- Beta-elimination of a side chain
- Formation of disulfide bonds
Correct Answer: Epimerization at the C-4 center
Q3. How does pH generally affect acid-catalyzed hydrolysis of susceptible antibiotics?
- Rate increases with decreasing pH (more acidic)
- Rate is independent of pH
- Rate increases only at very high pH
- Rate decreases with decreasing pH
Correct Answer: Rate increases with decreasing pH (more acidic)
Q4. Which kinetic order is most commonly observed for chemical degradation of antibiotics in dilute solution?
- Zero-order kinetics
- First-order kinetics
- Second-order kinetics
- Fractional-order kinetics
Correct Answer: First-order kinetics
Q5. For a first-order degradation process, which expression gives the half-life (t1/2)?
- t1/2 = 1 / k
- t1/2 = ln(2) / k
- t1/2 = k / ln(2)
- t1/2 = (ln k) / 2
Correct Answer: t1/2 = ln(2) / k
Q6. Which analytical technique is most powerful for identifying unknown antibiotic degradation products?
- LC–MS (liquid chromatography–mass spectrometry)
- Colorimetric titration
- Paper chromatography
- Simple UV spectrophotometry without separation
Correct Answer: LC–MS (liquid chromatography–mass spectrometry)
Q7. The primary objective of forced degradation studies in method development is to:
- Generate degradation products to validate a stability-indicating method and identify degradation pathways
- Determine tablet disintegration time only
- Measure solubility of the drug in different solvents
- Assess patient adherence under stress
Correct Answer: Generate degradation products to validate a stability-indicating method and identify degradation pathways
Q8. The best practical approach to protect a photosensitive antibiotic during storage is:
- Use amber or opaque packaging and minimize light exposure
- Store in clear glass under fluorescent light
- Expose to sunlight intermittently to “harden” the product
- Keep at room temperature in transparent blister packs
Correct Answer: Use amber or opaque packaging and minimize light exposure
Q9. Trace metal ions often accelerate antibiotic degradation by catalyzing which process?
- Oxidation via redox cycling
- Physical adsorption without reaction
- Recrystallization into a more stable form
- Polymerization of the API
Correct Answer: Oxidation via redox cycling
Q10. Which antioxidant is commonly used in formulations to inhibit oxidative degradation?
- Sodium metabisulfite
- Hydrogen peroxide
- Chloramine-T
- Sodium hypochlorite
Correct Answer: Sodium metabisulfite
Q11. Why is lyophilization (freeze-drying) used for some antibiotic formulations?
- To remove water and improve chemical stability
- To increase photodegradation
- To convert API into toxic impurities
- To make formulations more hygroscopic
Correct Answer: To remove water and improve chemical stability
Q12. The Arrhenius equation is used in stability studies to:
- Extrapolate rate constants to different temperatures to predict shelf-life
- Determine pH of maximum stability directly
- Measure light intensity during photostability testing
- Calculate melting point of the drug
Correct Answer: Extrapolate rate constants to different temperatures to predict shelf-life
Q13. Which excipient class can promote Maillard-type degradation with amine-containing antibiotics?
- Reducing sugars such as lactose
- Surfactants like polysorbate 80
- Inert fillers like microcrystalline cellulose
- Non-reducing polymers such as PEG 4000
Correct Answer: Reducing sugars such as lactose
Q14. A stability-indicating analytical method must:
- Separate the intact drug from its degradation products and quantify the drug selectively
- Only quantify total UV-absorbing species
- Ignore impurities under all conditions
- Be based solely on visual inspection
Correct Answer: Separate the intact drug from its degradation products and quantify the drug selectively
Q15. Photostability testing per ICH Q1B requires exposure to:
- Specified UV and visible light to evaluate photodegradation
- Only infrared radiation
- Gamma irradiation exclusively
- Ultrasound waves
Correct Answer: Specified UV and visible light to evaluate photodegradation
Q16. Oxidative degradation of antibiotics is commonly promoted by:
- Oxygen and trace metal catalysts
- Anoxic, metal-free conditions
- Low temperatures only
- Highly reducing atmospheres
Correct Answer: Oxygen and trace metal catalysts
Q17. Hydrolysis of penicillins typically yields which major degradation product?
- Penicilloic acid
- 4-epitetracycline
- Sulfoxide derivative
- Dehydrocefuroxime
Correct Answer: Penicilloic acid
Q18. What does the term “pseudo-first-order” mean in degradation kinetics?
- One reactant is in large excess so the rate appears first-order with respect to the antibiotic
- The reaction is actually zero-order but misreported
- Rate depends on the square of the concentration
- The rate constant changes randomly over time
Correct Answer: One reactant is in large excess so the rate appears first-order with respect to the antibiotic
Q19. Which storage conditions generally minimize hydrolytic degradation of an aqueous antibiotic?
- Low temperature and low humidity
- High temperature and high humidity
- Room temperature with sunlight exposure
- Freezing and repeated thaw cycles
Correct Answer: Low temperature and low humidity
Q20. Epimerization refers to:
- Conversion to an isomer with inversion of configuration at a single stereocenter
- Loss of a functional group by hydrolysis
- Oxidation of a sulfur atom to sulfoxide
- Polymer linkage formation between API molecules
Correct Answer: Conversion to an isomer with inversion of configuration at a single stereocenter
Q21. To minimize hydrolysis of an acid-labile drug, formulators should:
- Adjust formulation pH to the region of maximum drug stability
- Always use pH 2 regardless of drug chemistry
- Include excessive water to dilute the drug
- Store exclusively at pH equal to drug pKa
Correct Answer: Adjust formulation pH to the region of maximum drug stability
Q22. Oxidation of sulfur-containing antibiotics commonly yields which transformation?
- Formation of sulfoxide (or further to sulfone)
- Production of penicilloic acid
- Epimerization at adjacent stereocenters
- Polymerization into insoluble aggregates
Correct Answer: Formation of sulfoxide (or further to sulfone)
Q23. Why are chelating agents like EDTA added to some antibiotic formulations?
- To bind trace metal ions that catalyze oxidative degradation
- To increase moisture content intentionally
- To act as primary antioxidants by scavenging free radicals
- To reduce solubility dramatically
Correct Answer: To bind trace metal ions that catalyze oxidative degradation
Q24. Which analytical metric demonstrates that a method can resolve drug from its impurities?
- Resolution and peak purity showing separation of drug and degradation peaks
- Only the sensitivity (LOD/LOQ)
- Only the run time
- Only visual color change
Correct Answer: Resolution and peak purity showing separation of drug and degradation peaks
Q25. Which antibiotic class is notably susceptible to photodegradation?
- Tetracyclines
- Aminoglycosides
- Glycopeptides
- Polymyxins
Correct Answer: Tetracyclines
Q26. How does the pKa of an antibiotic influence its chemical stability?
- Ionization state (relative to pH) affects susceptibility to hydrolysis and other pathways
- pKa only affects taste, not stability
- Lower pKa always gives better stability
- Higher pKa always gives worse solubility
Correct Answer: Ionization state (relative to pH) affects susceptibility to hydrolysis and other pathways
Q27. Which type of preservative/excipient is most likely to promote antibiotic degradation?
- Oxidizing preservatives (e.g., peroxide-containing agents)
- Non-ionic surfactants under inert atmosphere
- Pharmacologically inert cellulose fillers
- High molecular weight PEG that is pure and stable
Correct Answer: Oxidizing preservatives (e.g., peroxide-containing agents)
Q28. Which experimental result confirms an HPLC method is stability-indicating?
- Complete separation of API peak from degradation product peaks and passing peak purity tests
- Short retention time regardless of separation
- Single peak observed for all stressed samples
- Only UV spectrum matches without chromatographic separation
Correct Answer: Complete separation of API peak from degradation product peaks and passing peak purity tests
Q29. How can selection of a salt form influence antibiotic chemical stability?
- Salt form alters solubility and microenvironmental pH, affecting degradation rates
- Salt forms have no effect on chemical stability
- Salt selection only affects color, not reactivity
- All salts always accelerate degradation equally
Correct Answer: Salt form alters solubility and microenvironmental pH, affecting degradation rates
Q30. Which ICH guideline specifically provides general guidance on stability testing of new drug substances and products?
- ICH Q1A(R2) — Stability Testing of New Drug Substances and Products
- ICH Q3C — Impurities: Residual Solvents
- ICH Q6A — Specifications: Test Procedures and Acceptance Criteria
- ICH M4 — Common Technical Document (CTD)
Correct Answer: ICH Q1A(R2) — Stability Testing of New Drug Substances and Products
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.
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