Application of Multi-criteria Decision Making Approach and Experimental Design and Development of Stability-indicating UPLC Method for Simultaneous Determination of Losartan Potassium and Hydrochlorothiazide in Bulk and Tablet Dosage Form

Abstract

This paper describes a multi response optimization methodology in combination with experimental design as a powerful technique for development of a RP-UPLC method for the simultaneous determination of losartan potassium and hydrochlorothiazide in combined dosage forms. The response surface design by means of 24 full factorial design was used taking resolution, symmetry of two peaks, and two retention factors as the responses with four important factors, pH of the mobile phase, percentage of the organic modifier, buffer concentration and column temperature, were used to design mathematical models. Derringer’s desirability function was used for reaching a suitable compromise among the responses. Optimal conditions included mobile phase consisting of acetonitrile–acetate buffer 38:62 v/v, pH 5.25 and buffer concentration of 28 mM as the mobile phase and at a flow rate of 0.3 ml/min and a column temperature of 37°C. The calibration plot was linear over the concentration ranges of 0.05–7 µg/mL for Losartan and 0.0125-4 µg/mL for hydrochlorothiazide having correlation coefficients not less than 0.999. Limits of detection and quantification were 0.287, 0.869 µg/mL and 0.487, 1.47 µg/mL, for Losartan and hydrochlorothiazide respectively. The specificity and stability-indicating capability of the method was proven through forced degradation studies, which showed no interference of the excipients. The robustness of the method was evaluated by Youden and Steiner’s robustness test. The method is simple, rapid, and robust for simultaneous determination of losartan potassium and hydrochlorothiazide with minimum amount of solvent mobile phase and shortest run time about 4.5 min.