Development and validation of high performance liquid chromatographic and derivative spectrophotometric methods for the determination of candesartan cilexetil in pharmaceutical forms

Abstract

In this work, two simple and fast methods for the determination of candesartan cilexetil in pharmaceutical forms, having it as a sole drug, were developed and validated. Candesartan cilexetil is a prodrug hydrolyzed to candesartan during absorption from the gastrointestinal tract. Candesartan is a selective AT1 subtype angiotensin II receptor antagonist used in the management of hypertension. The HPLC method uses a Chromolith RP-18e column. The mobile phase is acetonitrile - 0.1 % trifluoroacetic acid aqueous solution in ratio 50.0:50.0 (v/v) in an isocratic elution at a flow rate of 1.5 mL min -1. The diode array detector is operated at 251 nm, and column temperature is set to 20° C. The UV-derivative spectrophotometric method is based in the linear relation between drug concentration and first-order derivative spectrophotometric measurement. Alkaline aqueous solutions (0.1 M NaOH) of candesartan cilexetil exhibit a maximum at 246 nm and a minimum at 263 nm (1D 248-263). The sum of these two absolute values is the signal used on the range concentration 6.34 mg L -1 to 25.34 mg L -1. The accuracy of the method, as mean recovery percent, is 98.9 % and the relative standard deviation, 0.76 %. Both methods were validated according to parameters established for specificity, linearity, precision, accuracy, stability and limits of quantification and detection. The limits of detection and quantification, chromatographic parameters and selectivity obtained are better than other published methods. These methods were applied for the content uniformity of solid dosage pharmaceutical forms of two commercial brands.