Development and Validation of a Novel RP-HPLC Method for Estimation of Losartan Potassium in Dissolution Samples of Immediate and Sustained Release Tablets
A simple, rapid, selective, and reproducible reversed-phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for the estimation of Losartan potassium in dissolution samples of Losartan potassium immediate and sustained release tablets. Analysis was performed on an Agilent, Zorbax Eclipse XDB C18 column (150？mm × 4.6？mm, 5？μm) with the mobile phase consisting of orthophosphoric acid (0.1% v/v)—acetonitrile (55？:？45, v/v) at a flow rate of 1.0？mL/min. UV detection was performed at 225？nm and the retention time for Losartan was about 2.6 minutes. The calibration curve was linear (correlation coefficient = 0.999) in the selected range of analyte. The optimized dissolution conditions include the USP apparatus 2 at a paddle rotation rate of 50？rpm and 900？mL of pH 6.8 phosphate buffer as dissolution medium, at °C. The method was validated for precision, linearity, specificity, accuracy, limit of quantitation, and ruggedness. The system suitability parameters, such as theoretical plate, tailing factor and relative standard deviation (RSD) between five standard replicates, were well within the limits. The stability result shows that the drug is stable in the prescribed dissolution medium. 1. Introduction Dissolution is an official test routinely used in Quality Control (QC) and Research and Development (R and D) Laboratories for the evaluation of pharmaceutical products. The purpose of in vitro dissolution studies in QC is to check batch to batch consistency and detection of manufacturing deviation while in R and D the focus is to provide some predictive estimate of the drug release in respect to the in vivo performance of a drug product [1]. Losartan potassium is chemically 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-yl-phenyl)benzyl]-imidazole-5-methanol monopotassium salt (Figure 1) [2]. It is an angiotensin II receptor blocker and chemically is used as an antihypertensive agent [3]. Losartan has been demonstrated to be superior to previous peptide receptor antagonists and angiotensin converting enzyme (ACE) inhibitors because of its enhanced specificity, selectivity, and tolerability [4]. Currently, Losartan potassium is marketed alone or combined with hydrochlorothiazide. Figure 1: Chemical structure of Losartan potassium [ 28]. Several analytical methods have been applied to the analysis of Losartan potassium in pharmaceutical products that make use of high performance thin layer chromatography (HPTLC) [5, 6], capillary electrophoresis (CE), capillary electrochromatography (CEC) [7], and spectrophotometry [8–10]. The
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