Micellar Electrokinetic Chromatography (MEKC) with Multiresponse Chemometric Optimization for the Determination of Hydrochlorothiazide and Coformulated Antihypertensives in the Presence of Hydrochlorothiazide Major Impurity

Abstract

In this work, micellar electrokinetic chromatographic method was developed and optimized for the determination of hydrochlorothiazide (HCT) in the presence of irbesartan (IRB), bisoprolol (BISO) and HCT main impurity. Four factors affecting the separation - sodium dodecyl sulphate (SDS) concentration, buffer concentration, temperature and voltage - were studied. Optimization studies were performed with the aid of a central composite design with six central points. The optimal separation conditions were obtained by applying Derringer's desirability function, and the conditions were borate buffer 17 mM (pH = 9), SDS 5.2 mM, temperature 25°C and voltage 12 kV. HCT, IRB and BISO were successfully determined in their pure form and pharmaceutical formulations with separation in <8 min. Calibration curves (R > 0.999) were prepared and complete method validation was performed according to ICH guidelines. The results obtained were statistically compared with that of the official methods.