Pharmaceutical Analysis and Quality Control: Methods, Validation and Calculations
Pharmaceutical Analysis and Quality Control tests the theory and calculation of pharmacopoeial methods, instrumental analysis and validation - the backbone of drug testing by a Drug Inspector.
Core rules
- Titrimetry: acid–base, non-aqueous (perchloric acid in glacial acetic acid for weak bases), redox, complexometric (EDTA) and iodometric methods; calculate normality, molarity and percentage purity.
- Beer–Lambert: A = εbc = A(1%,1 cm) × c(% w/v) × b; linearity is verified over a defined range and λmax is chosen for sensitivity.
- Chromatography: HPLC system suitability includes retention time, resolution (Rs ≥ 2), tailing factor (≤ 2), theoretical plates and relative standard deviation (often ≤ 2%).
- Validation (ICH Q2): specificity, linearity and range, accuracy, precision, detection limit (3.3σ/S), quantitation limit (10σ/S) and robustness.
- Dissolution: apparatus 1 (basket) and 2 (paddle), with Q values and tolerance tables; media and speed are pharmacopoeial.
Worked example
A drug has A(1%, 1 cm) = 500 at its λmax. A sample solution gives absorbance 0.500 in a 1 cm cell. Then c(% w/v) = 0.500/500 = 0.001% w/v, which is 0.001 g per 100 mL, i.e. 10 µg/mL. Dilution factors must be applied before comparing with the label claim.
Traps
Do not report LOD as LOQ; do not treat precision as accuracy; do not omit system suitability before an assay; and never compare an absorbance reading with a label claim without accounting for dilution and any salt-to-base conversion factor.