Chemometric optimization of a SIA promethazine hydrochloride assay method

A sequential injection analysis (SIA) method for the assay of promethazine hydrochloride, based on its oxidation by acidified cerium(IV), was optimized. Three chemometric approaches were applied: (i) factorial design (3³ applied to surface plot and 2³ applied to effect factor) for screening the potential interacting variables, (ii) univariant for optimizing insignificantly interacting variables and (iii) simplex for optimizing potentially interacting variables. The optimum experimental conditions were 30 μl of 0.38 mol/l sulphuric acid, 30 μl of 3.99 × 10^{- 3} mol/l cerium(IV), 20 μl of promethazine hydrochloride and 20 μl/s flow rate. The detection limit was 7.032 × 10^{- 5} mol/l and the calibration curve was linear up to 1.563 mol/l with a correlation coefficient 0.9998, accuracy range of 89.0-101.5%, relative standard deviation 1.1% (n = 10) and sample frequency at least 20 samples/h. The method was applied to tablet form and validated with the British Pharmacopoeia method. The developed SIA method is fully automated, reproducible, sensitive, rapid and reagent-saving, and therefore suitable for routine control in tablets form.