Benzoic acid derivatives, especially benzoyl esters, play a crucial role in the chemistry and forensic analysis of cocaine. Cocaine is a tropane alkaloid with a benzoyl ester (derived from benzoic acid) and a methyl ester on the ecgonine scaffold; these functional groups determine synthesis strategies, physicochemical properties, metabolism to benzoylecgonine, and analytical detectability. B.Pharm students should understand benzoylation reactions (benzoyl chloride), ester hydrolysis by plasma esterases, stereochemistry of the tropane ring, salt versus free-base behavior, pharmacodynamics (local anesthetic, sodium-channel blockade; sympathomimetic effects), and instrumental methods (GC-MS, HPLC, immunoassays) used in forensic toxicology. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which functional group in cocaine is directly derived from benzoic acid?
- Benzoyl ester
- Benzyl alcohol
- Benzamide
Correct Answer: Benzoyl ester
Q2. What is the primary urinary metabolite of cocaine used in forensic screening?
- Benzoylecgonine
- Ecgonine methyl ester
- Norcocaine
- Cocaethylene
Correct Answer: Benzoylecgonine
Q3. Which enzyme class is chiefly responsible for the rapid plasma hydrolysis of cocaine’s ester bonds?
- Cytochrome P450 oxidases
- Monoamine oxidases
- Plasma butyrylcholinesterase (esterases)
- Alcohol dehydrogenase
Correct Answer: Plasma butyrylcholinesterase (esterases)
Q4. The local anesthetic effect of cocaine is primarily due to blockade of which ion channel?
- Voltage-gated calcium channels
- Voltage-gated sodium channels
- Ligand-gated chloride channels
- Potassium leak channels
Correct Answer: Voltage-gated sodium channels
Q5. Structurally, cocaine is best described as which of the following?
- A benzoyl ester of ecgonine
- A benzyl ether of tropane
- An amide of benzoic acid
- A benzoic acid salt
Correct Answer: A benzoyl ester of ecgonine
Q6. Which reagent is commonly used to introduce the benzoyl group during classical laboratory synthesis of cocaine analogs?
- Benzoyl chloride
- Benzaldehyde
- Benzene diazonium salt
- Benzoyl peroxide
Correct Answer: Benzoyl chloride
Q7. Which analytical technique provides the most definitive confirmation of cocaine in a seized sample?
- Color spot tests
- Immunoassay screening
- Gas chromatography–mass spectrometry (GC‑MS)
- Thin-layer chromatography (TLC)
Correct Answer: Gas chromatography–mass spectrometry (GC‑MS)
Q8. Which compound is formed when cocaine is metabolized in the presence of ethanol and is associated with increased toxicity?
- Benzoylecgonine
- Cocaethylene
- Ecgonine
- Norcocaine
Correct Answer: Cocaethylene
Q9. The tertiary amine in cocaine has an approximate pKa. Which value is closest?
- 3.2
- 7.4
- 8.6
- 11.5
Correct Answer: 8.6
Q10. Which statement correctly contrasts cocaine hydrochloride (salt) with free-base (“crack”)?
- Cocaine hydrochloride is water-soluble; free-base is volatile and smokable
- Free-base is water-soluble; hydrochloride is volatile and smokable
- Both forms have identical volatility and solubility
- Hydrochloride converts to benzoylecgonine on heating
Correct Answer: Cocaine hydrochloride is water-soluble; free-base is volatile and smokable
Q11. Hydrolysis of the methyl ester of cocaine yields which structural change to produce benzoylecgonine?
- Removal of the benzoyl group to form an alcohol
- Conversion of the methyl ester to a carboxylic acid
- Oxidation of the tropane nitrogen to an N-oxide
- Addition of a sulfate group
Correct Answer: Conversion of the methyl ester to a carboxylic acid
Q12. How many stereocenters are present in the standard natural cocaine molecule?
- 1
- 2
- 3
- 4
Correct Answer: 4
Q13. Which reagent would efficiently saponify the benzoyl ester of cocaine under laboratory conditions?
- Sodium hydroxide (NaOH)
- Hydrochloric acid (HCl)
- Hydrogen peroxide (H2O2)
- Potassium permanganate (KMnO4)
Correct Answer: Sodium hydroxide (NaOH)
Q14. In infrared spectroscopy of cocaine, the ester carbonyl typically gives a strong absorption near which wavenumber?
- ~1200 cm−1
- ~1500 cm−1
- ~1735 cm−1
- ~3300 cm−1
Correct Answer: ~1735 cm−1
Q15. Cocaine primarily increases synaptic levels of which neurotransmitter by inhibiting reuptake?
- GABA
- Dopamine
- Acetylcholine
- Glutamate
Correct Answer: Dopamine
Q16. Immunoassay screens for cocaine exposure in urine most commonly target which analyte?
- Parent cocaine only
- Benzoylecgonine-specific antibodies (benzoylecgonine)
- Benzoic acid
- Ecgonine methyl ester exclusively
Correct Answer: Benzoylecgonine-specific antibodies (benzoylecgonine)
Q17. N‑demethylation of cocaine to norcocaine is mediated primarily by which enzyme family?
- Carboxylesterases
- Cytochrome P450 enzymes (e.g., CYP3A4)
- Monoamine oxidases
- Glutathione S-transferases
Correct Answer: Cytochrome P450 enzymes (e.g., CYP3A4)
Q18. Which description best matches the aqueous solubility of cocaine hydrochloride?
- Practically insoluble in water
- Highly water-soluble
- Sparingly soluble unless heated above 80°C
- Soluble only in organic solvents
Correct Answer: Highly water-soluble
Q19. The basic center responsible for protonation of cocaine under physiological pH is which functional group?
- Primary alcohol
- Tertiary amine in the tropane ring
- Benzoyl carbonyl oxygen
- Methyl ester oxygen
Correct Answer: Tertiary amine in the tropane ring
Q20. Which analytical technique is most suitable to resolve and quantify enantiomers of cocaine or analogs?
- Normal-phase TLC
- Chiral HPLC
- UV‑Vis spectrophotometry
- Unmodified GC with achiral column
Correct Answer: Chiral HPLC
Q21. Co-ingestion of ethanol with cocaine most commonly leads to which pharmacological consequence?
- Formation of benzoylecgonine with reduced toxicity
- Formation of cocaethylene with increased cardiotoxicity and prolonged effects
- Complete inactivation of cocaine via glucuronidation
- Immediate precipitation of cocaine as insoluble salt
Correct Answer: Formation of cocaethylene with increased cardiotoxicity and prolonged effects
Q22. What is the primary effect of the benzoyl (benzoic acid–derived) group on cocaine’s physicochemical properties?
- Greatly increases basicity of the molecule
- Increases lipophilicity and membrane permeability
- Converts cocaine into a strong oxidizing agent
- Makes the molecule fluorescent under UV
Correct Answer: Increases lipophilicity and membrane permeability
Q23. In the United States, cocaine is classified under which controlled substance schedule for medical use and abuse potential?
- Schedule I
- Schedule II
- Schedule III
- Schedule IV
Correct Answer: Schedule II
Q24. Which presumptive color spot test is commonly used in the field to indicate possible presence of cocaine?
- Mandelin test
- Scott test (cobalt thiocyanate)
- Biuret test
- Ferric chloride test
Correct Answer: Scott test (cobalt thiocyanate)
Q25. Further hydrolysis of benzoylecgonine ultimately yields which core scaffold (small molecule) derived from ecgonine metabolism?
- Benzoic acid only
- Ecgonine
- Para-hydroxybenzaldehyde
- Phenylacetic acid
Correct Answer: Ecgonine
Q26. Which sample preparation technique is widely preferred to extract cocaine and metabolites from biological matrices prior to instrumental analysis?
- Direct injection without cleanup
- Solid-phase extraction (SPE)
- Dialysis against buffer
- Protein crystallization
Correct Answer: Solid-phase extraction (SPE)
Q27. Compared with procaine, cocaine’s higher local anesthetic potency is mainly attributed to which factor?
- Lower molecular weight
- Greater lipophilicity due to the benzoyl group
- Higher water solubility
- Presence of a primary amine
Correct Answer: Greater lipophilicity due to the benzoyl group
Q28. The benzoic acid released from metabolic breakdown of benzoyl groups is commonly conjugated in the liver to form which urinary metabolite?
- Hippuric acid
- Salicylic acid
- Phenylglyoxylic acid
- Glucuronic acid only
Correct Answer: Hippuric acid
Q29. Which intermediate scaffold is central to most semi‑synthetic approaches to cocaine and its analogs?
- Scopolamine
- Ecgonine
- Atropine
- Nicotine
Correct Answer: Ecgonine
Q30. Which statement about detection windows is correct in routine urine drug testing?
- Parent cocaine is detected longer than benzoylecgonine
- Benzoylecgonine is detectable in urine longer than parent cocaine
- Cocaethylene is never detectable in urine
- Ecgonine is the sole long-term marker used in standard screenings
Correct Answer: Benzoylecgonine is detectable in urine longer than parent cocaine
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