Pharmaceutical Analysis: Titrimetry, Spectroscopy, Chromatography and Validation
Pharmaceutical Analysis in GPAT covers titrimetry, spectroscopy, chromatography, instrumentation and validation. Questions test calculation discipline and the correct technique for a sample type.
Core techniques
- Titrimetry: acid–base, redox, complexometric, non-aqueous; calculate from molarity × volume × stoichiometry.
- UV–Vis: Beer–Lambert A = εbc; linear range, quartz cells below 340 nm.
- HPLC: reversed-phase C18 is common; retention increases with hydrophobicity; system suitability includes tailing factor, resolution and theoretical plates.
- IR identifies functional groups; NMR gives connectivity; MS gives molecular mass and fragments.
Validation
ICH Q2 parameters: accuracy, precision, specificity, LOD, LOQ, linearity, range and robustness. LOD/LOQ are based on signal-to-noise or standard deviation of response and slope.
Worked example
A 0.500 g sample is titrated with 24.50 mL of 0.1000 M NaOH (1:1 stoichiometry, MW 180.16). Moles = 0.02450 L × 0.1000 mol/L = 0.002450 mol. Mass = 0.002450 × 180.16 = 0.4414 g. Percentage = (0.4414/0.500) × 100 = 88.28% w/w. The blank and indicator correction are assumed negligible here.
Traps
Using normality and molarity interchangeably; forgetting the dilution factor; reporting assay on an as-is basis when the monograph requires dried basis; validating linearity with a single point.