Pharmaceutical Chemistry and Analysis: Assay, Validation and Stability
This domain tests pharmacopoeial quality control: identification, purity and limit tests, assay by titrimetry and instrumental methods, method validation, and stability. Expect calculations and interpretation of acceptance criteria rather than pure theory.
Core toolkit
- Pharmacopoeial monograph: description, solubility, identification, tests for related substances, assay and storage.
- Titrimetry: direct acid–base, redox, complexometric and non-aqueous methods; calculate from molarity, stoichiometry and sample mass.
- Instrumental analysis: UV-Vis (Beer–Lambert), HPLC (system suitability, calibration), potentiometry, Karl Fischer for water.
- Validation: specificity, linearity, accuracy, precision, LOD/LOQ and robustness under ICH Q2.
- Stability: ICH Q1A conditions; degradation by hydrolysis, oxidation and photolysis; Arrhenius extrapolation supports but does not replace real-time shelf-life data.
Worked example
A 0.4500 g sample of a drug (MW 180.16, reacting 1:1 with NaOH) required 24.50 mL of 0.1000 M NaOH. Moles NaOH = 0.02450 × 0.1000 = 2.450 × 10⁻³ mol. Mass of drug = 2.450 × 10⁻³ × 180.16 = 0.4414 g. Purity = 0.4414/0.4500 × 100 = 98.1%. Reasoning: confirm stoichiometry, use the correct equivalent weight, and report to appropriate significant figures.
Traps
Using molecular weight when the reaction is 2:1; forgetting the blank titration; applying a dried-basis result to an undried sample; reporting 98.09% from data that justify only three significant figures; confusing LOD with LOQ; treating accelerated stability as proof of long-term shelf-life.