Chromatographic method development for the simultaneous assay of pseudoephedrine hydrochloride and chlorphenamine maleate in oral dosage formulations

Common cold medicines usually present as multi-component products and constitute one of the largest groups of ‘over-the-counter’ medicines marketed in Ghana. Due to their wide patronage and easy accessibility, their quality control is of utmost importance to medicine consumers. In this study, the Design of Experiment (DOE) concept is adopted to develop a chromatographic method for the simultaneous assay of pseudoephedrine hydrochloride and chlorphenamine maleate in commercially available products. The separation of the drugs was achieved on an Agilent Eclipse Plus C18 analytical column (4.6 × 150 mm; 5 µm) and detected at 252 nm, while maintaining column temperature at 30 oC. The method parameters, including acetonitrile concentration in the mobile phase, mobile phase pH and flow rate were optimized using a Central Composite Design study, while monitoring the method attributes, asymmetric factors, selectivity, retention times, and resolution. The outcome showed a good correlation between experimental and predictive values throughout the modeled Design Space, with a Desirability of 1.000. The conditions optimized included a mobile phase containing acetonitrile, 50 mM aqueous acetate buffer solution (pH = 3.19) and triethylamine (15.34:84.65:0.01 v/v/v), and a flow rate of 1.437 mL/min. The method was then validated following the International Council for Harmonization Q2(R) guidelines to establish linearity and range, accuracy, precision, robustness, and stability of the test solution. The developed method was successfully applied to estimate pseudoephedrine hydrochloride and chlorphenamine maleate contents in single and fixed-dose formulations commercially available (N = 38).