Podophyllotoxin is an aryltetralin lignan extracted from Podophyllum, Dysosma and Sinopodophyllum species and serves as a key precursor for semisynthetic anticancer agents like etoposide and teniposide. Industrial production combines optimized plant extraction (solvent selection, maceration, Soxhlet, SFE), plant cell culture and semi-synthesis to meet pharmaceutical demand. Quality control using HPLC, TLC, NMR and mass spectrometry, along with GMP-compliant processing, residual solvent testing and impurity profiling ensures safety and efficacy. Understanding biosynthesis, extraction yield optimization, scale-up challenges, environmental impact and regulatory requirements is essential for B.Pharm students focused on natural product drug development. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which plant genera are the primary commercial sources of podophyllotoxin?
- Podophyllum, Dysosma, Sinopodophyllum
- Aloe, Artemisia, Digitalis
- Cinchona, Taxus, Camptotheca
- Rauwolfia, Atropa, Papaver
Correct Answer: Podophyllum, Dysosma, Sinopodophyllum
Q2. Podophyllotoxin belongs to which class of natural products?
- Alkaloids
- Sesquiterpenes
- Aryltetralin lignans
- Flavonoids
Correct Answer: Aryltetralin lignans
Q3. What is the primary industrial role of podophyllotoxin?
- Direct use as an oral chemotherapeutic agent
- Precursor for semisynthetic anticancer drugs
- Primary active for antihypertensive drugs
- Food additive and flavoring agent
Correct Answer: Precursor for semisynthetic anticancer drugs
Q4. Which extraction technique uses supercritical CO2 to extract podophyllotoxin?
- Steam distillation
- Supercritical fluid extraction (SFE)
- Soxhlet extraction with ethanol
- Maceration with water
Correct Answer: Supercritical fluid extraction (SFE)
Q5. Which solvent property is most important when selecting a solvent to extract podophyllotoxin?
- High acidity (pH < 2)
- Polarity and solubility for lignans
- High ionic strength
- Ability to form chelates with metals
Correct Answer: Polarity and solubility for lignans
Q6. Which analytical method is the gold standard for quantitative assay and purity profiling of podophyllotoxin in industry?
- Thin-layer chromatography (TLC)
- High-performance liquid chromatography (HPLC)
- Paper chromatography
- Colorimetric titration
Correct Answer: High-performance liquid chromatography (HPLC)
Q7. Podophyllotoxin’s semisynthetic derivative etoposide primarily inhibits which cellular target?
- Tubulin polymerization at the colchicine site
- Topoisomerase II
- DNA methyltransferase
- RNA polymerase II
Correct Answer: Topoisomerase II
Q8. What is the main mechanism of action of parent podophyllotoxin (not etoposide)?
- Inhibition of microtubule assembly by binding tubulin
- Covalent DNA alkylation
- Inhibition of thymidylate synthase
- Antimetabolite blocking purine synthesis
Correct Answer: Inhibition of microtubule assembly by binding tubulin
Q9. Which scale-up challenge is especially relevant for plant-derived podophyllotoxin production?
- Maintaining identical pH across batches
- Variability in raw plant material podophyllotoxin content
- Availability of synthetic starting materials only
- Excessive photostability of the compound
Correct Answer: Variability in raw plant material podophyllotoxin content
Q10. Which process is used industrially to convert podophyllotoxin into etoposide?
- Direct fermentation by fungi
- Semi-synthetic chemical modification
- Hydrogenation to reduce aromatic rings
- Purely enzymatic conversion in vivo
Correct Answer: Semi-synthetic chemical modification
Q11. Which quality control parameter is critical for assessing solvent residues after podophyllotoxin extraction?
- Melting point determination
- Residual solvent analysis (e.g., GC)
- Optical rotation only
- Visual color inspection
Correct Answer: Residual solvent analysis (e.g., GC)
Q12. Which chromatographic technique is commonly used for initial fractionation of podophyllotoxin from crude extracts?
- Gas chromatography with FID
- Column chromatography on silica gel
- Ion-exchange chromatography
- Affinity chromatography using antibodies
Correct Answer: Column chromatography on silica gel
Q13. Plant cell culture approaches to produce podophyllotoxin aim to address which issue?
- Inability to chemically synthesize lignans
- Conservation and sustainability of wild plant populations
- Reducing basic research costs
- Creating edible formulations
Correct Answer: Conservation and sustainability of wild plant populations
Q14. Which spectroscopic method provides structural confirmation and stereochemistry information for podophyllotoxin?
- UV-Vis spectroscopy only
- NMR spectroscopy
- Flame photometry
- Refractometry
Correct Answer: NMR spectroscopy
Q15. Why is stereochemistry important in podophyllotoxin semisynthesis?
- Stereochemistry only affects color, not activity
- Biological activity and conversion efficiency depend on stereochemistry
- Stereochemistry is irrelevant for lignans
- It only affects solubility in water
Correct Answer: Biological activity and conversion efficiency depend on stereochemistry
Q16. Which environmental concern is significant in industrial podophyllotoxin extraction?
- Excess oxygen generation
- Solvent waste and phytochemical-rich effluents
- Noise pollution from shaker incubators
- Overproduction of CO2 during crystallization
Correct Answer: Solvent waste and phytochemical-rich effluents
Q17. Which clinical topical use is podophyllotoxin directly approved for?
- Systemic chemotherapy of leukemia
- Topical treatment of genital warts (condyloma acuminata)
- Oral treatment for hypertension
- Inhalation therapy for asthma
Correct Answer: Topical treatment of genital warts (condyloma acuminata)
Q18. Which regulatory requirement is essential for pharmaceutical-grade podophyllotoxin production?
- ISO food safety certification only
- GMP compliance and validated analytical methods
- No documentation if source is natural
- Only local agricultural permits
Correct Answer: GMP compliance and validated analytical methods
Q19. Which strategy can increase podophyllotoxin yield in plant cell cultures?
- Use of elicitors and precursors to boost biosynthesis
- Strict dark incubation without nutrients
- Elimination of all growth regulators
- Use of tap water instead of media
Correct Answer: Use of elicitors and precursors to boost biosynthesis
Q20. Which impurity profiling technique helps identify unknown degradation products of podophyllotoxin?
- Gravimetric analysis
- LC-MS/MS (liquid chromatography–mass spectrometry)
- pH titration only
- Simple paper chromatography
Correct Answer: LC-MS/MS (liquid chromatography–mass spectrometry)
Q21. What is a common solvent used in Soxhlet extraction of podophyllotoxin from dried rhizomes?
- Hexane only
- Acetonitrile exclusively
- Alcohols like methanol or ethanol
- Pure water at room temperature
Correct Answer: Alcohols like methanol or ethanol
Q22. Which downstream processing step is important to crystallize purified podophyllotoxin?
- Lyophilization from strong base
- Solvent evaporation followed by recrystallization
- Direct freeze-drying of crude extract without solvent removal
- Filtration through activated charcoal only
Correct Answer: Solvent evaporation followed by recrystallization
Q23. Which safety concern is associated with handling podophyllotoxin in production?
- It is a strong respiratory irritant at all concentrations
- It is cytotoxic and can cause local tissue damage
- It is non-toxic and requires no PPE
- It causes immediate combustion on contact with air
Correct Answer: It is cytotoxic and can cause local tissue damage
Q24. Which metabolic engineering goal could reduce reliance on plant harvesting for podophyllotoxin?
- Engineering microbes or plants to overproduce podophyllotoxin or precursors
- Suppressing lignan biosynthesis completely
- Deleting all genes involved in podophyllotoxin pathway
- Engineering microbes to degrade podophyllotoxin
Correct Answer: Engineering microbes or plants to overproduce podophyllotoxin or precursors
Q25. Which parameter is NOT typically part of stability studies for podophyllotoxin drug substances?
- Temperature and humidity effects
- Photostability under light exposure
- Magnetic susceptibility in MRI fields
- Forced degradation under oxidative conditions
Correct Answer: Magnetic susceptibility in MRI fields
Q26. Which technique helps in rapid screening of podophyllotoxin content in multiple plant samples?
- High-throughput HPLC or UPLC assays
- Single-sample NMR only
- Gas chromatography without derivatization for nonvolatile lignans
- Manual paper chromatography for each sample
Correct Answer: High-throughput HPLC or UPLC assays
Q27. Which chemical feature distinguishes podophyllotoxin-class lignans?
- Steroidal tetracyclic core
- Aryltetralin skeleton with methylenedioxy and lactone elements
- Simple benzene ring without oxygenation
- Linear peptide backbone
Correct Answer: Aryltetralin skeleton with methylenedioxy and lactone elements
Q28. Which formulation is used for topical podophyllotoxin therapy?
- 0.5% podophyllotoxin cream or solution
- 100% pure podophyllotoxin paste applied systemically
- Intravenous podophyllotoxin infusion
- Inhalable aerosol suspension
Correct Answer: 0.5% podophyllotoxin cream or solution
Q29. Which biotechnological approach can enable continuous production of podophyllotoxin derivatives?
- Batch extraction from wild-harvested plants only
- Continuous fermentation using engineered microbial cell factories
- Solar evaporation of rhizome juices
- Manual synthesis by individual artisans
Correct Answer: Continuous fermentation using engineered microbial cell factories
Q30. Which factor is most critical when developing an industrial process for podophyllotoxin that must meet regulatory approval?
- High aesthetic appearance of the final crystals
- Robust validated process with reproducible purity, safety and documentation
- Minimal employee training to reduce costs
- Exclusive use of novel unvalidated analytical methods
Correct Answer: Robust validated process with reproducible purity, safety and documentation
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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