Urea and monoacylureas are important nitrogenous functional groups in medicinal chemistry, affecting solubility, hydrogen bonding and drug metabolism. This concise guide links core concepts of urea chemistry—structure, synthesis (Wöhler, industrial ammoniation of CO2), acylation to form monoacylureas, reactivity and analytical identification—with clinical and formulation aspects relevant to carbamazepine. Carbamazepine, a dibenzazepine anticonvulsant, undergoes CYP3A4-mediated oxidation and shows autoinduction, interactions and characteristic stability issues that impact formulation, bioavailability and safety. B. Pharm students will find targeted revision points covering synthesis, reaction mechanisms, spectral identification, pharmacokinetics and quality control. Practical MCQs below reinforce application of theory to pharmaceutical analysis, formulation and therapeutics. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which of the following is the correct molecular formula of urea?
- CH4N2O
- CO(NH2)2
- NH2CONH
- CH3CONH2
Correct Answer: CO(NH2)2
Q2. The classical laboratory synthesis of urea from ammonium cyanate is known as which reaction?
- Bucherer reaction
- Wöhler synthesis
- Fischer esterification
- Ullmann coupling
Correct Answer: Wöhler synthesis
Q3. Monoacylureas are best described as which structural type?
- R–NH–CO–NH–R’ (both nitrogens acylated)
- R–CO–NH–CO–NH2 (one nitrogen acylated)
- R–NH–CO–OR’ (urethane)
- R–NH–NH–CO–R’ (hydrazide)
Correct Answer: R–CO–NH–CO–NH2 (one nitrogen acylated)
Q4. Industrial production of urea primarily involves which reagents under high pressure?
- Ammonia and carbon monoxide
- Ammonia and carbon dioxide
- Ammonium sulfate and CO2
- Nitrogen and methane
Correct Answer: Ammonia and carbon dioxide
Q5. Acylation of urea to form N-acylureas typically uses which acylating agent in the laboratory?
- Acyl chloride
- Diazonium salt
- Grignard reagent
- Sodium borohydride
Correct Answer: Acyl chloride
Q6. Which IR absorption band is diagnostic for the carbonyl group in ureas and monoacylureas?
- Around 2100 cm-1
- Around 1700 cm-1
- Around 3300 cm-1
- Around 1500 cm-1
Correct Answer: Around 1700 cm-1
Q7. Compared with simple amides, ureas generally exhibit which of the following due to additional hydrogen bonding?
- Lower melting point and lower solubility
- Higher melting point and higher water solubility
- No hydrogen bonding, thus similar properties
- Decreased polarity and increased lipophilicity
Correct Answer: Higher melting point and higher water solubility
Q8. In 13C NMR spectroscopy, the carbonyl carbon of a monoacylurea typically appears in which chemical shift region?
- 0–50 ppm
- 50–80 ppm
- 120–150 ppm
- 160–180 ppm
Correct Answer: 160–180 ppm
Q9. Which reagent can convert a substituted urea into an isocyanate under dehydrating conditions (useful in synthetic sequences)?
- PCl5 or POCl3
- Sodium borohydride
- KMnO4
- HCl (dilute)
Correct Answer: PCl5 or POCl3
Q10. Monoacylureas can be intermediates in the synthesis of which pharmaceutical functional group by subsequent transformations?
- Carboxylic acids by oxidation
- Urethanes via alcoholysis
- Thioureas via sulfurization
- Hydantoins by cyclization
Correct Answer: Hydantoins by cyclization
Q11. Which statement correctly describes hydrogen bonding capacity of urea?
- Urea is only a hydrogen bond donor
- Urea is only a hydrogen bond acceptor
- Urea can act as both hydrogen bond donor and acceptor
- Urea cannot participate in hydrogen bonding
Correct Answer: Urea can act as both hydrogen bond donor and acceptor
Q12. Which of the following tests is commonly used to detect free isocyanate contaminants that may form during acylation reactions of urea?
- HPLC with UV detection only
- Colorimetric test with dibutylamine
- Reaction with 2,4-dinitrophenylhydrazine (DNPH)
- IR monitoring for strong N=C=O stretch near 2270 cm-1
Correct Answer: IR monitoring for strong N=C=O stretch near 2270 cm-1
Q13. What is a common pharmaceutical relevance of arylurea derivatives?
- They are exclusively used as solvents
- They serve as antihypertensives only
- They act as herbicides and as drug leads (e.g., kinase inhibitors)
- They are inert excipients with no bioactivity
Correct Answer: They act as herbicides and as drug leads (e.g., kinase inhibitors)
Q14. Hydrolysis of monoacylureas under strongly acidic conditions typically yields which pair of products?
- Amine and ester
- Amine and carbon dioxide
- Urea and carboxylic acid
- Amide and alcohol
Correct Answer: Urea and carboxylic acid
Q15. Which pH condition favors the solubility of unsubstituted urea in aqueous media?
- Highly acidic (pH 1)
- Neutral pH (around 7)
- Highly basic (pH 13)
- pH has negligible effect because urea is neutral
Correct Answer: pH has negligible effect because urea is neutral
Q16. In chromatographic analysis, monoacylureas compared to parent urea generally show what behavior on reversed-phase HPLC?
- Elute earlier due to higher polarity
- Elute later due to increased hydrophobicity
- Co-elute exactly with urea
- Cannot be analyzed by reversed-phase HPLC
Correct Answer: Elute later due to increased hydrophobicity
Q17. Which reagent combination is commonly used to acylate urea selectively to form N-monoacylurea (one acylation) rather than diacylation?
- Large excess of acyl chloride and strong base
- Acyl chloride in presence of stoichiometric urea and low temperature
- Heat urea with acid anhydride at reflux for long time
- Perform acylation under strongly basic aqueous conditions
Correct Answer: Acyl chloride in presence of stoichiometric urea and low temperature
Q18. For quality control of monoacylureas, which spectral feature helps distinguish N-acylation from O-acylation?
- Appearance of a new N–H stretch at 3500 cm-1
- Shift of carbonyl absorption to higher frequency and loss of urea N–H signal patterns
- Complete disappearance of all C–H stretches
- Emergence of a strong C–O stretch at 1200 cm-1
Correct Answer: Shift of carbonyl absorption to higher frequency and loss of urea N–H signal patterns
Q19. Which property of urea makes it a common denaturant in protein studies and formulation science?
- Strong hydrophobicity destabilizes proteins
- Poor solubility in water prevents interactions
- Ability to disrupt hydrogen bonding networks in proteins
- Reactive carbocation formation
Correct Answer: Ability to disrupt hydrogen bonding networks in proteins
Q20. In synthetic planning, monoacylureas are advantageous intermediates because:
- They are extremely volatile and easy to remove
- They are inert and cannot be transformed further
- They can undergo intramolecular cyclizations to heterocycles
- They always decompose on mild heating
Correct Answer: They can undergo intramolecular cyclizations to heterocycles
Q21. Which of the following is a common impurity class to monitor when synthesizing monoacylureas?
- Peroxides
- Unreacted acyl chloride and diacylureas
- Alkyl halides
- Sulfonic acids
Correct Answer: Unreacted acyl chloride and diacylureas
Q22. N-acylation of urea is thermodynamically favored under which circumstance?
- When acyl group is strongly electron donating
- When acylating reagent is activated (e.g., acid chloride) and nucleophile is deprotonated
- When reaction is carried out in water at ambient temperature only
- When urea is converted to a diazonium intermediate first
Correct Answer: When acylating reagent is activated (e.g., acid chloride) and nucleophile is deprotonated
Q23. Urea derivatives are often tested for stability under accelerated conditions. Which parameter is most indicative of hydrolytic degradation?
- Decrease in melting point
- Increase in water content only
- Appearance of carboxylic acid impurities by HPLC
- Change in refractive index
Correct Answer: Appearance of carboxylic acid impurities by HPLC
Q24. Which analytical technique best differentiates monoacylurea positional isomers (N1- vs N3-acylation)?
- Simple melting point measurement
- 1H and 15N NMR combined with 2D correlations
- Thin layer chromatography only
- UV-visible spectroscopy
Correct Answer: 1H and 15N NMR combined with 2D correlations
Q25. Which safety precaution is particularly important when handling acyl chlorides for urea acylation?
- Avoid peroxide formation
- Use inert atmosphere and acid scavenger to neutralize HCl
- Protect from light only
- Store at high temperature to prevent solidification
Correct Answer: Use inert atmosphere and acid scavenger to neutralize HCl
Q26. Carbamazepine belongs to which chemical class?
- Barbiturates
- Dibenzazepine (tricyclic) derivative
- Benzodiazepine
- Hydantoin
Correct Answer: Dibenzazepine (tricyclic) derivative
Q27. The primary mechanism of action of carbamazepine in epilepsy is:
- Enhancement of GABA-A receptor chloride currents
- Blockade of voltage-gated sodium channels
- Inhibition of monoamine oxidase
- NMDA receptor agonism
Correct Answer: Blockade of voltage-gated sodium channels
Q28. Carbamazepine is metabolized primarily to which active metabolite?
- N-desmethylcarbamazepine
- Carbamazepine-10,11-epoxide
- Carbamazepine glucuronide only
- Iminostilbene alcohol
Correct Answer: Carbamazepine-10,11-epoxide
Q29. Which cytochrome P450 isoenzyme is mainly responsible for carbamazepine oxidation?
- CYP2D6
- CYP3A4
- CYP1A2
- CYP2C19
Correct Answer: CYP3A4
Q30. Carbamazepine exhibits autoinduction. What does this mean?
- It inhibits its own metabolism leading to accumulation
- It induces enzymes that increase its own metabolism over time
- It causes auto-oxidation in solid dosage forms
- It forms a stable adduct with plasma proteins
Correct Answer: It induces enzymes that increase its own metabolism over time
Q31. The therapeutic plasma concentration range commonly cited for carbamazepine is:
- 0.5–2 μg/mL
- 4–12 μg/mL
- 20–40 μg/mL
- 50–100 μg/mL
Correct Answer: 4–12 μg/mL
Q32. One serious dermatologic adverse reaction linked to carbamazepine is strongly associated with the HLA-B*1502 allele. Which population is this allele most prevalent in?
- East Asian populations (e.g., Han Chinese)
- European Caucasian populations
- Native South American populations
- Sub-Saharan African populations only
Correct Answer: East Asian populations (e.g., Han Chinese)
Q33. Which laboratory test is essential before initiating carbamazepine in patients at risk of blood dyscrasias?
- Liver function test only
- Complete blood count with differential
- Urine culture
- Blood glucose
Correct Answer: Complete blood count with differential
Q34. Carbamazepine can cause hyponatremia via which mechanism?
- Renal tubular necrosis
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- Direct sodium channel blockade in the kidney
- Increased sodium dietary loss only
Correct Answer: Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Q35. For stability-indicating HPLC assay of carbamazepine, a key degradation product to monitor is:
- Acetaminophen
- Carbamazepine-10,11-epoxide
- Phenobarbital
- Imipramine
Correct Answer: Carbamazepine-10,11-epoxide
Q36. Which formulation strategy is commonly used to improve the bioavailability of poorly water-soluble carbamazepine?
- Converting to a very large tablet without excipients
- Formulating as solid dispersions or using cyclodextrin complexes
- Adding urea directly as a filler
- Administering as a simple aqueous injection
Correct Answer: Formulating as solid dispersions or using cyclodextrin complexes
Q37. Which drug interaction is expected when carbamazepine is co-administered with oral contraceptives?
- Carbamazepine increases contraceptive levels, enhancing efficacy
- Carbamazepine induces metabolism and may reduce contraceptive effectiveness
- No interaction is expected
- Contraceptives cause autoinduction of carbamazepine
Correct Answer: Carbamazepine induces metabolism and may reduce contraceptive effectiveness
Q38. Which adverse effect is most characteristic of carbamazepine overdose?
- Severe hypoglycemia
- Cerebellar signs such as ataxia and nystagmus
- Profound hypertension only
- Immediate anaphylaxis in all patients
Correct Answer: Cerebellar signs such as ataxia and nystagmus
Q39. Which analytical method is the pharmacopoeial standard for assay and impurity profiling of carbamazepine tablets?
- Infrared spectroscopy only
- High-performance liquid chromatography (HPLC)
- TLC with UV lamp only
- Colorimetric titration
Correct Answer: High-performance liquid chromatography (HPLC)
Q40. Carbamazepine demonstrates which of the following physical properties relevant to formulation?
- Highly water soluble and hygroscopic
- Poor water solubility and moderate lipophilicity
- Extremely volatile compound
- Strongly basic with pKa around 4
Correct Answer: Poor water solubility and moderate lipophilicity
Q41. Which of these is a common synthetic impurity or related substance of carbamazepine to be controlled in quality control?
- Carbamazepine-10,11-epoxide
- 2,4-dinitrophenylhydrazone
- Urea
- Acetaldehyde
Correct Answer: Carbamazepine-10,11-epoxide
Q42. Which storage condition is recommended to minimize carbamazepine degradation in solid dosage forms?
- High temperature and high humidity
- Protected from light, cool and dry conditions
- Exposed to sunlight for photostabilization
- Stored in alkaline aqueous solution
Correct Answer: Protected from light, cool and dry conditions
Q43. A patient starting carbamazepine should be counseled about which early warning sign requiring immediate attention?
- Dry mouth only
- Development of rash, mucosal lesions or blistering
- Mild headache for one day
- Temporary hair color change
Correct Answer: Development of rash, mucosal lesions or blistering
Q44. Co-administration of carbamazepine with which drug is likely to increase carbamazepine plasma levels due to CYP inhibition?
- Rifampicin
- Phenytoin
- Ketoconazole
- Phenobarbital
Correct Answer: Ketoconazole
Q45. In terms of ionization, carbamazepine is best described as:
- Strongly basic (pKa ~8)
- Neutral under physiological pH with non-ionizable amide
- Strongly acidic (pKa ~3)
- Quaternary ammonium salt at neutral pH
Correct Answer: Neutral under physiological pH with non-ionizable amide
Q46. Which parameter is most affected by carbamazepine autoinduction during chronic therapy?
- Volume of distribution decreases dramatically
- Half-life decreases over time as clearance increases
- Absorption rate becomes zero-order only
- Bioavailability becomes infinite
Correct Answer: Half-life decreases over time as clearance increases
Q47. In formulation development, why is particle size reduction a useful strategy for carbamazepine?
- It decreases surface area and slows dissolution
- It increases surface area to enhance dissolution rate and bioavailability
- It converts the drug to a liquid form
- It always prevents polymorphic changes
Correct Answer: It increases surface area to enhance dissolution rate and bioavailability
Q48. Which clinical indication is carbamazepine commonly used for, besides epilepsy?
- Diabetes mellitus type 2
- Trigeminal neuralgia and bipolar disorder
- Acute bacterial infections
- Hypothyroidism
Correct Answer: Trigeminal neuralgia and bipolar disorder
Q49. During stability testing, photodegradation of carbamazepine can lead to which change detectable by HPLC?
- Formation of new unknown peaks corresponding to photoproducts
- Complete disappearance of the solvent peak only
- No changes detectable by HPLC ever
- Immediate precipitation of all excipients
Correct Answer: Formation of new unknown peaks corresponding to photoproducts
Q50. Which patient counseling point is important when initiating carbamazepine therapy?
- There are no interactions with other medications
- Report any signs of infection, unusual bruising or bleeding, and any skin rash promptly
- It is safe to combine with grapefruit juice daily without concern
- No need for any blood monitoring during therapy
Correct Answer: Report any signs of infection, unusual bruising or bleeding, and any skin rash promptly
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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