Stability-Indicating Reversed-Phase Liquid Chromatographic Method for Simultaneous Determination of Simvastatin and Ezetimibe from Their Combination Drug Products

Abstract

A simple, precise, and rapid stability-indicating reversed-phase column liquid chromatographic (RP-LC) method has been developed and subsequently validated for simultaneous estimation of atorvastatin (ATV) and ezetimibe (EZE) from their combination drug product. The proposed RP-LC method utilizes a LiChrospher 100 C18, 5 microm, 250 x 4.0 mm id column at ambient temperature; the optimum mobile phase consists of acetonitrile-water-methanol (45 + 40 + 15, v/v/v) with apparent pH adjusted to 4.0 +/- 0.1; mobile phase flow rate of 1.0 mL/min; and UV detection at 250 nm. ATV, EZE, and their combination drug product were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. There were no other coeluting, interfering peaks from excipients, impurities, or degradation products due to variable stress conditions, and the method is specific for the estimation of ATV and EZE in the presence of degradation products. The response was linear over the concentration range of 1-80 microg/mL for ATV and EZE. The mean recoveries were 99.27 and 98.5% for ATV and EZE, respectively. The intermediate precision data were obtained under different experimental conditions, and the calculated value of the coefficient of variation was found to be less than the critical value. The proposed method can be useful in the quality control of bulk manufacturing and pharmaceutical dosage forms.