Non-aqueous titration is an essential analytical technique in pharmaceutical analysis where titrations are carried out in solvents other than water to determine weak acids or bases, or substances insoluble in aqueous media. Key principles include careful solvent selection (protic vs. aprotic), control of moisture, understanding protolytic equilibria, choice of suitable titrants (e.g., perchloric acid in glacial acetic acid), and endpoint detection by visual indicators or potentiometric methods. Applications for B. Pharm students include assay and purity testing of alkaloids, barbiturates, sulfonamides and other drugs, stability studies, and formulation analysis. Mastery of standardization, indicator selection and solvent effects ensures accurate results. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the main reason for using non-aqueous titration in pharmaceutical analysis?
- To speed up titrations by increasing reaction rates
- To analyse weak acids or bases insoluble or undissociated in water
- To avoid using toxic reagents
- To increase volatility of analytes
Correct Answer: To analyse weak acids or bases insoluble or undissociated in water
Q2. Which solvent is most commonly used with perchloric acid for titration of weak bases?
- Absolute ethanol
- Glacial acetic acid
- Dimethyl sulfoxide (DMSO)
- Water
Correct Answer: Glacial acetic acid
Q3. Which titrant is typically used for non-aqueous titration of weak acids in methanol?
- Sodium hydroxide in water
- Perchloric acid in acetic acid
- Sodium methoxide in methanol
- Hydrochloric acid in ethanol
Correct Answer: Sodium methoxide in methanol
Q4. Why must moisture be rigorously excluded in many non-aqueous titrations?
- Because water increases the solubility of indicators
- Because water can change solvent acidity and alter the titration reaction
- Because water decreases titrant concentration only slightly
- Because water speeds up color change of indicators
Correct Answer: Because water can change solvent acidity and alter the titration reaction
Q5. Which statement about proton transfer in non-aqueous media is correct?
- Acid–base strength order is identical to that in water
- Protic non-aqueous solvents do not participate in proton transfer
- Solvent properties strongly influence apparent acid and base strengths
- Autoionization of solvent is negligible and irrelevant
Correct Answer: Solvent properties strongly influence apparent acid and base strengths
Q6. Which indicator is commonly used for titration of weak bases with perchloric acid in acetic acid?
- Phenolphthalein
- Crystal violet
- Methyl orange
- Phenol red
Correct Answer: Crystal violet
Q7. For analytes that give no clear color change with indicators, which endpoint detection is preferred?
- Gravimetric detection
- Potentiometric titration
- Ultraviolet absorption only
- Visual turbidity
Correct Answer: Potentiometric titration
Q8. What is the role of a co-solvent (e.g., dichloromethane) in some non-aqueous titrations?
- To neutralize the titrant
- To increase sample volatility
- To improve solubility of analyte and adjust solvent polarity
- To provide water for ionization
Correct Answer: To improve solubility of analyte and adjust solvent polarity
Q9. Which pharmaceutical compound class is frequently analysed by non-aqueous titration?
- Strong inorganic salts
- Alkaloids (weak bases)
- Highly water-soluble sugars
- Gaseous anesthetics
Correct Answer: Alkaloids (weak bases)
Q10. What is one major advantage of non-aqueous titration over aqueous titration?
- Requires no standardization of titrants
- Permits titration of substances that are too weakly ionized in water
- Always gives sharper endpoints than potentiometry
- Is unaffected by atmospheric CO2
Correct Answer: Permits titration of substances that are too weakly ionized in water
Q11. Which property of the solvent most strongly affects the position of equilibrium in non-aqueous acid–base titrations?
- Boiling point
- Dielectric constant and proton-donating ability
- Viscosity
- Color
Correct Answer: Dielectric constant and proton-donating ability
Q12. In a non-aqueous titration, the term “leveling effect” refers to:
- The solvent causing all acids to have the same observable strength
- The equal volume of titrant added at each step
- The balancing of ionic strength by electrolyte addition
- The smoothing of titration curve by stirring
Correct Answer: The solvent causing all acids to have the same observable strength
Q13. Which preparation step is critical before performing a non-aqueous titration?
- Heating the solvent to boiling
- Removal of water by drying solvents and glassware
- Addition of excess water to ensure solubility
- Exposing sample to air to equilibrate
Correct Answer: Removal of water by drying solvents and glassware
Q14. Which titration technique is often used for drugs that decompose near the endpoint color change?
- Acid–base back titration
- Potentiometric titration
- Turbidimetric titration
- Thermometric titration only
Correct Answer: Potentiometric titration
Q15. During standardization of perchloric acid in acetic acid, which primary standard might be used?
- Potassium hydrogen phthalate (KHP)
- Sodium chloride
- Benzoic acid
- Tripotassium phosphate
Correct Answer: Potassium hydrogen phthalate (KHP)
Q16. What is a common limitation of using visual indicators in non-aqueous titrations?
- Indicators are universally stable in all non-aqueous solvents
- Indicator color range may shift or be suppressed by solvent color or acidity
- Indicators always give a sharp endpoint in non-aqueous media
- Indicator choice does not affect accuracy
Correct Answer: Indicator color range may shift or be suppressed by solvent color or acidity
Q17. In non-aqueous titration, why is perchloric acid often preferred as a titrant for bases?
- It is a weak, nonreactive acid
- It acts as a strong acid in many organic solvents, giving a sharp endpoint
- It is less hazardous than hydrochloric acid
- It is insoluble in organic solvents
Correct Answer: It acts as a strong acid in many organic solvents, giving a sharp endpoint
Q18. Which monitoring method provides the titration curve for non-aqueous titrations?
- Conductometric titration
- Potentiometric titration (electrode potential vs volume)
- Refractometric titration only
- Visual estimation without instruments
Correct Answer: Potentiometric titration (electrode potential vs volume)
Q19. For titration of very weakly basic drugs, which solvent system can increase basicity detection?
- Highly protic, strongly ionizing solvents like water
- Non-polar solvents with no proton activity
- Glacial acetic acid (a protic organic solvent)
- Pure hydrocarbon solvents like hexane
Correct Answer: Glacial acetic acid (a protic organic solvent)
Q20. What is an appropriate approach if the analyte is only partially soluble in the chosen non-aqueous solvent?
- Add a small proportion of a compatible co-solvent to improve solubility
- Add water to dissolve the analyte fully
- Proceed without complete dissolution; endpoint unaffected
- Use solid titration methods only
Correct Answer: Add a small proportion of a compatible co-solvent to improve solubility
Q21. Which of the following is a typical application of non-aqueous titration in quality control?
- Determining water content in hydrophilic gels
- Assay of basic pharmaceutical actives such as quinine or codeine
- Analysis of volatile solvents by GC only
- Determination of particle size distribution
Correct Answer: Assay of basic pharmaceutical actives such as quinine or codeine
Q22. Which electrode is commonly used for potentiometric detection in non-aqueous acid–base titrations?
- Silver/silver chloride electrode only
- Glass pH electrode adapted for non-aqueous media or combination electrodes
- Thermocouple
- Reference electrode without a sensing electrode
Correct Answer: Glass pH electrode adapted for non-aqueous media or combination electrodes
Q23. Why might back titration be preferred in some non-aqueous procedures?
- Back titration avoids the need for solvent drying
- It is useful when direct titration endpoints are slow or indistinct
- It eliminates titrant standardization
- It reduces reagent consumption to zero
Correct Answer: It is useful when direct titration endpoints are slow or indistinct
Q24. Which safety consideration is particularly important when using perchloric acid in organic solvents?
- Perchloric acid in organic media is non-oxidizing and safe
- Perchloric acid can form explosive perchlorate salts and requires special handling
- Perchloric acid neutralizes spontaneously on contact with air
- Perchloric acid is completely safe at room temperature
Correct Answer: Perchloric acid can form explosive perchlorate salts and requires special handling
Q25. How is the strength of acids/bases expressed differently in non-aqueous media compared to aqueous?
- Only pH is used in both media with same scale
- Acidity functions or solvent-specific pKa-like concepts are used due to solvent effects
- No concept of acidity exists in non-aqueous media
- Concentration alone determines strength regardless of solvent
Correct Answer: Acidity functions or solvent-specific pKa-like concepts are used due to solvent effects
Q26. Which of the following is an advantage of potentiometric titration in non-aqueous systems?
- It eliminates the need to control moisture
- Provides an objective and reproducible endpoint even when indicators fail
- It requires no calibration or maintenance of electrodes
- It always shortens titration time
Correct Answer: Provides an objective and reproducible endpoint even when indicators fail
Q27. What is the effect of a strongly protic solvent on the apparent basicity of an organic base?
- It always makes the base behave as a stronger acid
- It can enhance protonation, making bases appear stronger
- It has no effect on protonation equilibria
- It converts bases into neutral species
Correct Answer: It can enhance protonation, making bases appear stronger
Q28. When performing a non-aqueous titration, why is titrant standardization necessary?
- Titrants are always perfectly stable and need no standardization
- Standardization ensures accurate concentration due to solvent interactions and reagent aging
- Standardization is only needed for aqueous titrations
- It is required to change the color of the titrant
Correct Answer: Standardization ensures accurate concentration due to solvent interactions and reagent aging
Q29. Which factor most often causes broad or ill-defined endpoints in non-aqueous visual titrations?
- Use of a perfectly dry solvent
- Strong, sharp acid–base reactions
- Indicator–solvent incompatibility or low indicator sensitivity
- Using an excess of titrant
Correct Answer: Indicator–solvent incompatibility or low indicator sensitivity
Q30. Which practice improves accuracy when transferring small volumes of non-aqueous titrant?
- Use air to expel titrant from the burette rapidly
- Use properly calibrated glassware, avoid moisture ingress, and rinse with titrant
- Rinse burette with water before titration
- Store titrant-burette assembly in open air
Correct Answer: Use properly calibrated glassware, avoid moisture ingress, and rinse with titrant
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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