Pharmaceutical Analysis and Quality Assurance: Titrations, Spectroscopy, Validation
What the domain tests
This domain tests quantitative technique - volumetric and instrumental methods - plus the validation framework that decides whether a result is legally usable. Expect calculations from Beer–Lambert law, titration stoichiometry, LOD/LOQ and chromatographic system suitability, along with knowledge of ICH Q2 parameters.
Core rules to hold
- Non-aqueous titration: weak bases titrated with perchloric acid in glacial acetic acid using crystal violet; weak acids with sodium methoxide in dimethylformamide using thymol blue.
- Complexometric titration: disodium EDTA with mordant black 11 for calcium and magnesium; masking agents for selectivity.
- Redox methods: iodimetry (direct, with standard iodine) and iodometry (liberated iodine titrated with thiosulphate, starch indicator) for oxidising drugs.
- Beer–Lambert law: A = εbc; chromophores absorb, auxochromes intensify; a bathochromic shift moves λmax to longer wavelength.
- Validation per ICH Q2: specificity, linearity and range, accuracy, precision (repeatability, intermediate, reproducibility), detection and quantification limits, robustness.
- LOD and LOQ: LOD = 3.3σ/S and LOQ = 10σ/S, where σ is the standard deviation of the response and S the slope.
Worked example
A solution in a 1 cm cell has absorbance 0.45 at its λmax, and the molar absorptivity is 150 L mol⁻¹ cm⁻¹. Rearranging A = εbc gives c = 0.45/(150 × 1) = 0.003 mol/L, that is 3 mmol/L. Note that absorbance is dimensionless and linearity fails above roughly 1.0, so dilutions must keep readings within the validated range.
Traps that cost marks
Swapping the 3.3 and 10 factors for LOD and LOQ; treating precision (agreement of replicates) as accuracy (closeness to truth); reporting an Rf value above 1; omitting the reagent blank in UV assays.