Diazotisation titration is a key analytical method in pharmaceutical analysis for quantifying diazotizable compounds, especially primary aromatic amines. B.Pharm students must grasp the chemical principle—generation of diazonium salts by nitrous acid under acidic, low-temperature conditions—and how this reaction is applied in titrations, endpoint detection, and quality control. Important keywords include diazotisation titration, nitrous acid, sodium nitrite, hydrochloric acid, azo coupling, indicators, stoichiometry, interfering substances, temperature control, sensitivity, accuracy and pharmaceutical assay. Understanding practical aspects, method validation and limitations enhances assay reliability and impurity profiling in drug analysis. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which reagents are typically combined to generate nitrous acid in a diazotisation titration?
- Sodium nitrite and hydrochloric acid
- Sodium nitrite and sodium hydroxide
- Nitric acid and aniline
- Sodium nitrate and sulfuric acid
Correct Answer: Sodium nitrite and hydrochloric acid
Q2. What is the primary analyte class determined by diazotisation titration in pharmaceutical analysis?
- Primary aromatic amines
- Secondary alcohols
- Carboxylic acids
- Aliphatic ketones
Correct Answer: Primary aromatic amines
Q3. At which temperature range is diazotisation typically carried out to ensure diazonium salt stability?
- 0–5 °C
- 20–25 °C
- 40–50 °C
- 60–70 °C
Correct Answer: 0–5 °C
Q4. Which process is commonly used to detect the endpoint in diazotisation titrations by producing a colored product?
- Azo coupling with a coupling reagent (e.g., β-naphthol)
- Precipitation with barium chloride
- Complexation with EDTA
- Formation of a metal-ligand complex with ferric ion
Correct Answer: Azo coupling with a coupling reagent (e.g., β-naphthol)
Q5. Why is acidic medium required for diazotisation reactions?
- To protonate nitrite and form nitrous acid (HNO2)
- To deprotonate the amine and increase nucleophilicity
- To oxidize the amine to a nitroso compound
- To precipitate interfering salts
Correct Answer: To protonate nitrite and form nitrous acid (HNO2)
Q6. Which of the following interferes most with diazotisation titration of primary aromatic amines?
- Phenolic compounds that undergo coupling
- Aliphatic hydrocarbons
- Inorganic chlorides at low concentration
- Sugars such as glucose
Correct Answer: Phenolic compounds that undergo coupling
Q7. What is a major limitation of diazotisation titration in routine pharmaceutical QC?
- Instability of diazonium salts at elevated temperature
- Lack of sensitivity to aromatic amines
- Excessive selectivity for tertiary amines
- Inability to be automated
Correct Answer: Instability of diazonium salts at elevated temperature
Q8. In an assay using diazotisation titration, which pH condition is most appropriate during formation of diazonium salt?
- Strongly acidic (pH ~1–3)
- Neutral (pH ~7)
- Weakly basic (pH ~8–9)
- Highly basic (pH >12)
Correct Answer: Strongly acidic (pH ~1–3)
Q9. Which indicator system is often used in conjunction with diazotisation to form a visible azo dye?
- Sulfanilic acid and N-(1-naphthyl)ethylenediamine (Griess-type)
- Phenolphthalein and sodium hydroxide
- Starch and iodine
- Alizarin red and calcium ions
Correct Answer: Sulfanilic acid and N-(1-naphthyl)ethylenediamine (Griess-type)
Q10. Which kinetic factor must be controlled to ensure reproducible diazotisation titration results?
- Reaction temperature and addition rate of nitrite
- Ambient light exposure only
- Stirring speed exclusively
- Evaporation rate of solvent
Correct Answer: Reaction temperature and addition rate of nitrite
Q11. Which type of amine does NOT form a stable diazonium salt under standard diazotisation conditions?
- Aliphatic primary amines
- Aromatic primary amines
- Electron-deficient anilines
- Para-substituted anilines with activating groups
Correct Answer: Aliphatic primary amines
Q12. For method validation of a diazotisation titration, which parameter is most critical to demonstrate?
- Specificity toward diazotizable aromatic amines
- pH stability of tertiary amines
- Volumetric flask calibration only
- Solubility of inorganic electrolytes
Correct Answer: Specificity toward diazotizable aromatic amines
Q13. Which safety consideration is important when performing diazotisation in the lab?
- Avoid drying diazonium salts as they can be explosive
- Store diazonium salts at ambient temperature in open containers
- Use concentrated organic solvents to stabilize diazonium salts
- No special precautions are required
Correct Answer: Avoid drying diazonium salts as they can be explosive
Q14. In a diazotisation titration, what is the role of cooling the reaction mixture?
- To stabilize the diazonium ion and prevent decomposition
- To increase the rate of nucleophilic substitution
- To evaporate excess solvent
- To precipitate inorganic by-products
Correct Answer: To stabilize the diazonium ion and prevent decomposition
Q15. Which pharmaceutical application commonly uses diazotisation titration principles?
- Assay of sulfonamide impurities and aromatic amine content
- Assay of inorganic phosphate in tablets
- Determination of triglycerides in oils
- Quantification of polysaccharides in suspensions
Correct Answer: Assay of sulfonamide impurities and aromatic amine content
Q16. How does the presence of nitrite in the sample affect diazotisation titration?
- It causes positive bias by consuming reagent and producing extra diazonium
- It has no effect on the titration
- It increases pH drastically
- It reduces the ionic strength only
Correct Answer: It causes positive bias by consuming reagent and producing extra diazonium
Q17. Which analytical technique is often used to confirm diazotisation titration results for complex samples?
- HPLC with UV detection of azo derivatives
- Gravimetric analysis of precipitates
- Direct potentiometric pH measurement only
- Viscosity measurement
Correct Answer: HPLC with UV detection of azo derivatives
Q18. What stoichiometric ratio is commonly assumed between nitrous acid (HNO2) and a primary aromatic amine during diazotisation?
- 1:1 molar ratio
- 2:1 HNO2 to amine ratio
- 1:2 HNO2 to amine ratio
- 3:1 molar ratio
Correct Answer: 1:1 molar ratio
Q19. Which sample preparation step is often necessary before diazotisation titration of a pharmaceutical dosage form?
- Extraction of the aromatic amine into aqueous acidic medium
- Direct analysis of solid tablets without dissolution
- Lyophilization to dryness
- High-temperature digestion at 120 °C
Correct Answer: Extraction of the aromatic amine into aqueous acidic medium
Q20. Which analytical interference can be minimized by selective derivatization before diazotisation titration?
- Coexisting phenols that also form colored coupling products
- Inorganic chloride salts
- Nonpolar hydrocarbons
- Dissolved oxygen
Correct Answer: Coexisting phenols that also form colored coupling products
Q21. Why is standardization of sodium nitrite solution important in diazotisation titration?
- To ensure accurate stoichiometric reagent concentration and result precision
- Because sodium nitrite is completely stable indefinitely
- To lower the pH of samples automatically
- To precipitate impurities
Correct Answer: To ensure accurate stoichiometric reagent concentration and result precision
Q22. Which analytical parameter is improved by using azo coupling for endpoint detection?
- Sensitivity through formation of strongly colored dyes
- Solubility of analyte in organic solvents
- Volatility of the diazonium salt
- Thermal stability of the sample
Correct Answer: Sensitivity through formation of strongly colored dyes
Q23. Which functional group on an aromatic ring increases the ease of diazotisation?
- Electron-donating groups like -OH or -NH2
- Strong electron-withdrawing groups like -NO2
- Aliphatic side chains only
- Halogen substituents exclusively
Correct Answer: Electron-donating groups like -OH or -NH2
Q24. What is the effect of organic solvents in the diazotisation medium?
- They can destabilize diazonium ions and change coupling efficiency
- They always increase diazonium stability
- They neutralize nitrous acid completely
- They are required to form diazonium salts
Correct Answer: They can destabilize diazonium ions and change coupling efficiency
Q25. Which measurement technique can quantify azo dye formed after diazotisation coupling with highest throughput?
- UV-Vis spectrophotometry
- Manual titration with phenolphthalein
- Gravimetric weighing of dye
- Flame photometry
Correct Answer: UV-Vis spectrophotometry
Q26. Which control experiment is useful to check specificity in a diazotisation titration method?
- Blank run with all reagents but without the target amine
- Heating sample to 80 °C only
- Replacing nitrite with nitrate without other changes
- Adding excess base to sample
Correct Answer: Blank run with all reagents but without the target amine
Q27. In regulatory contexts, why is monitoring aromatic amine impurities important in drugs?
- Some aromatic amines are toxic or carcinogenic and must be controlled
- They enhance drug flavor and must be maximized
- They increase tablet hardness only
- They are always inert and require no monitoring
Correct Answer: Some aromatic amines are toxic or carcinogenic and must be controlled
Q28. Which of the following is an appropriate corrective action if diazotisation endpoint is blurred due to matrix color?
- Use an instrumental detection method like UV-Vis for the azo dye
- Ignore the color and estimate visually
- Add more nitrite without control
- Increase temperature to 60 °C to clear color
Correct Answer: Use an instrumental detection method like UV-Vis for the azo dye
Q29. Which structural feature favors formation of a stable diazonium salt for analytical titration?
- Aromatic ring directly bonded to the primary amine
- Aliphatic chain attached to the amine nitrogen
- Tertiary amine nitrogen
- Amide linkage next to the nitrogen
Correct Answer: Aromatic ring directly bonded to the primary amine
Q30. For reliable diazotisation titration in the QC lab, which practice is essential?
- Strict control of temperature, reagent purity and validated endpoint detection
- Performing the titration at variable uncontrolled temperatures
- Using expired sodium nitrite without standardization
- Skipping blank and specificity checks
Correct Answer: Strict control of temperature, reagent purity and validated endpoint detection
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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