Stability indicating HPLC method for simultaneous determination of candesartan cilexetil and hydrochlorothiazide in pharmaceuticals

Abstract

A simple and specific HPLC method was developed for simultaneous determination of candesartan cilexetil and hydrochlorothiazide in pharmaceuticals. Method development was performed by using a Zobax SB CN column (4.6x150 mm, 5μm). The optimum conditions were in a mixture of acetonitrile and 10 mM phosphate buffer (pH 7.0, 32:68, v/v) with a flow rate of 1 mL/min, the column temperature at 25oC, and the UV detection at 254 nm. Hydrochlorothiazide and candesartan cilexetil were eluted at 2.65 and 8.21 min, respectively. The method was validated for linearity and range, accuracy, precision, and specificity according to ICH guidelines. Linearity was obtained in the range of 50 to 150% of target concentrations. Percent recovery was in the range of 99.1% to 101.0% for candesartan cilexetil and 99.4% to 100.2% for hydrochlorothiazide. The %RSD of intra- and inter-day precision for both drugs was less than 1.66% and 1.84%, respectively. A stability study of candesartan cilexetil and hydrochlorothiazide was conducted using the developed and validated HPLC method. The method proved to be stability indicating as it can analyze the drugs in the presence of their degradation products with a resolution of the critical peak pair of 1.5 and peak purity values of more than 990. The drugs were stressed under acid/base/neutral hydrolysis, oxidation, photolysis, and thermal degradation. Candesartan cilexetil was stable under neutral (water) hydrolysis, photolysis, and thermal degradation, but it degraded under acid (0.1 N HCl) and base (0.1 N NaOH) hydrolysis, and oxidation (30% H2O2). Similarly, hydrochlorothiazide was stable under oxidation (30% H2O2), photolysis, and thermal degradation, but it degraded under neutral, acid (1 N HCl), and base (1 N NaOH) hydrolysis. The method was successfully applied to analyze commercial drug products with %RSD of five replication of less than 0.80%.