Non-aqueous titrations are essential in pharmaceutical analysis for determining weak acids and bases that are insoluble or poorly ionized in water. Choosing the right solvent—glacial acetic acid, methanol, DMF, pyridine or mixtures—controls ionization, indicator response and titrant behavior. Key solvent properties include protic vs. aprotic character, dielectric constant, donor/acceptor numbers and autoprotolysis. Common titrants are perchloric acid in glacial acetic acid and sodium ethoxide in ethanol; endpoints may be visual (Hammett indicators) or potentiometric. Proper solvent selection, standardization, endpoint detection and safety/disposal are vital for accurate pharmaceutical assays. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the primary reason to perform a non-aqueous titration in pharmaceutical analysis?
- To increase reaction speed for all drugs
- To titrate substances that are insoluble or weakly ionized in water
- To avoid using indicators
- To reduce reagent costs
Correct Answer: To titrate substances that are insoluble or weakly ionized in water
Q2. Which solvent is most commonly used as the medium for non-aqueous acidimetry?
- Distilled water
- Glacial acetic acid
- Hexane
- Carbon tetrachloride
Correct Answer: Glacial acetic acid
Q3. What is the typical titrant used in non-aqueous acid-base titrations to determine basic pharmaceutical compounds?
- Sodium hydroxide in water
- Perchloric acid in glacial acetic acid
- Hydrochloric acid in ethanol
- Acetic acid in acetone
Correct Answer: Perchloric acid in glacial acetic acid
Q4. Which statement best describes an aprotic solvent in the context of non-aqueous titrations?
- It freely donates protons and increases acidity
- It does not donate protons, minimizing solvent protonation effects
- It always reacts with titrants to form salts
- It increases the dielectric constant above water
Correct Answer: It does not donate protons, minimizing solvent protonation effects
Q5. Why is the autoprotolysis constant (solvent ionization) important for non-aqueous titrations?
- It determines solvent boiling point
- It indicates solvent color changes during titration
- It governs the available proton activity and affects endpoint behavior
- It measures solvent viscosity
Correct Answer: It governs the available proton activity and affects endpoint behavior
Q6. Why must non-aqueous titration solvents be essentially anhydrous?
- Water improves endpoint sharpness
- Water reacts with titrants and alters titration chemistry and equivalence point
- Water increases indicator stability
- Water neutralizes the analyte intentionally
Correct Answer: Water reacts with titrants and alters titration chemistry and equivalence point
Q7. Indicator selection in non-aqueous titration primarily depends on which factor?
- Indicator cost only
- Indicator pKa or transition range in the chosen solvent
- Indicator solubility in water
- Indicator molecular weight
Correct Answer: Indicator pKa or transition range in the chosen solvent
Q8. The Hammett acidity function (H0) is used in non-aqueous titrations to:
- Measure solvent viscosity
- Quantify the effective acidity of very strong acidic media in non-aqueous solvents
- Determine the optical rotation of indicators
- Standardize volumetric flasks
Correct Answer: Quantify the effective acidity of very strong acidic media in non-aqueous solvents
Q9. Which visual indicator is commonly used for perchloric acid titrations in glacial acetic acid?
- Phenolphthalein
- Methyl orange
- Crystal violet
- Starch
Correct Answer: Crystal violet
Q10. For titrating weak bases in non-aqueous media, a common solvent mixture is:
- Glacial acetic acid mixed with ethanol
- Pure hexane
- Water and chloroform (1:1)
- Glycerol only
Correct Answer: Glacial acetic acid mixed with ethanol
Q11. How does the solvent dielectric constant affect non-aqueous titrations?
- Higher dielectric always reduces reaction rate
- Lower dielectric constant reduces ion dissociation, affecting equivalence point and solubility
- Dielectric constant is irrelevant in titrations
- It determines the color of the solution
Correct Answer: Lower dielectric constant reduces ion dissociation, affecting equivalence point and solubility
Q12. Which titration method is commonly used to assay basic drugs (e.g., tertiary amines) in pharmaceuticals?
- Acid-base titration using perchloric acid in glacial acetic acid
- Redox titration with potassium permanganate in water
- Complexometric titration with EDTA in chloroform
- Precipitation titration with silver nitrate in hexane
Correct Answer: Acid-base titration using perchloric acid in glacial acetic acid
Q13. One major advantage of non-aqueous titrations over aqueous titrations is:
- The ability to titrate very strong inorganic acids only
- The ability to titrate weak organic acids and bases without hydrolysis or ion suppression by water
- No need for standardization of titrants
- The absence of need for indicators
Correct Answer: The ability to titrate weak organic acids and bases without hydrolysis or ion suppression by water
Q14. Which of the following is a polar aprotic solvent commonly used in pharmaceutical non-aqueous work?
- Methanol
- Dimethylformamide (DMF)
- Water
- n-Hexane
Correct Answer: Dimethylformamide (DMF)
Q15. Why are many aqueous indicators like methyl orange often unsuitable in non-aqueous titrations?
- They dissolve too well in non-aqueous solvents
- Their pKa and color transition range shift drastically in non-aqueous media
- They become carcinogenic
- They react with titrants to form precipitates
Correct Answer: Their pKa and color transition range shift drastically in non-aqueous media
Q16. Which primary standard is commonly used to standardize perchloric acid solutions in glacial acetic acid?
- Potassium hydrogen phthalate (KHP)
- Benzoic acid
- Sodium carbonate
- Citric acid
Correct Answer: Benzoic acid
Q17. Nitrobenzene is sometimes used in non-aqueous titrations primarily because it:
- Is a strong base
- Acts as a co-solvent to dissolve non-polar organic analytes and stabilize transition colors
- Reacts with perchloric acid to form a stronger titrant
- Is miscible with water to remove moisture
Correct Answer: Acts as a co-solvent to dissolve non-polar organic analytes and stabilize transition colors
Q18. The donor number and acceptor number of a solvent influence:
- The solvent boiling point only
- The solvent’s ability to solvate cations and anions, affecting titration equilibria
- Only the color of indicators
- Whether the solvent is flammable
Correct Answer: The solvent’s ability to solvate cations and anions, affecting titration equilibria
Q19. For alkalimetry (determining acidic substances) in non-aqueous systems, a commonly used titrant is:
- Sodium ethoxide in ethanol
- Nitric acid in water
- Acetic acid in water
- Potassium permanganate in acetone
Correct Answer: Sodium ethoxide in ethanol
Q20. Why are indicators with appropriate transition ranges crucial in non-aqueous titrations?
- Because color changes are slower
- Because solvent effects shift indicator pKa, requiring suitable transition ranges to visualize the endpoint
- Because visual detection is always unreliable
- Because they prevent titrant decomposition
Correct Answer: Because solvent effects shift indicator pKa, requiring suitable transition ranges to visualize the endpoint
Q21. Which safety concern is most relevant when handling glacial acetic acid in the laboratory?
- It is non-flammable and inert
- It is corrosive, hygroscopic and can cause severe burns and fumes
- It rapidly polymerizes at room temperature
- It explodes on contact with air
Correct Answer: It is corrosive, hygroscopic and can cause severe burns and fumes
Q22. What is one advantage of potentiometric end-point detection in non-aqueous titrations?
- It eliminates the need for standard titrants
- It provides an objective, reproducible endpoint when visual indicators are unreliable
- It only works in aqueous media
- It always increases the titration speed tenfold
Correct Answer: It provides an objective, reproducible endpoint when visual indicators are unreliable
Q23. Pyridine is sometimes used as a solvent in non-aqueous titrations because it:
- Is a strong acid that protonates analytes
- Acts as a basic medium and proton acceptor for titration of very strong acids
- Is non-polar and dissolves lipids only
- Has a lower boiling point than water
Correct Answer: Acts as a basic medium and proton acceptor for titration of very strong acids
Q24. The “leveling effect” in solvent chemistry refers to:
- The ability of a solvent to evaporate uniformly
- The phenomenon where the strength of a strong acid or base is limited by the solvent’s own acid/base properties
- The uniform color of indicators in different solvents
- The equal solubility of salts in all solvents
Correct Answer: The phenomenon where the strength of a strong acid or base is limited by the solvent’s own acid/base properties
Q25. Why are non-aqueous titrations particularly important in pharmaceutical assay development?
- They increase the shelf-life of drugs
- They allow accurate assay of weakly ionizable or hydrophobic drug substances and excipients without hydrolysis
- They replace chromatographic methods entirely
- They require no training to perform
Correct Answer: They allow accurate assay of weakly ionizable or hydrophobic drug substances and excipients without hydrolysis
Q26. Which solvent is classified as polar protic and often used in non-aqueous titrations?
- Methanol
- Carbon tetrachloride
- Dimethyl sulfoxide (DMSO)
- Benzene
Correct Answer: Methanol
Q27. How does residual water in a non-aqueous titration solvent affect accuracy?
- It usually improves endpoint sharpness
- It can hydrolyze analytes, consume titrant and shift equivalence points, reducing accuracy
- It has no measurable effect
- It completely prevents titration from proceeding
Correct Answer: It can hydrolyze analytes, consume titrant and shift equivalence points, reducing accuracy
Q28. Which concentration unit is frequently used and reported in non-aqueous titrations in pharmaceutical analysis?
- Molality (m)
- Normality (N)
- Parts per million (ppm)
- Mole fraction
Correct Answer: Normality (N)
Q29. How are pKa values affected when measured in non-aqueous solvents compared to water?
- They remain identical to aqueous pKa
- They shift and are highly solvent-dependent, often differing substantially from aqueous values
- They become irrelevant and cannot be measured
- They always decrease by 7 units
Correct Answer: They shift and are highly solvent-dependent, often differing substantially from aqueous values
Q30. Which pharmaceutical determination is commonly carried out by non-aqueous titration?
- Assay of free fatty acid (acid value) in oils and creams
- Total microbial count
- Particle size distribution
- Moisture by Karl Fischer only
Correct Answer: Assay of free fatty acid (acid value) in oils and creams
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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