Stability-indicating RP-UPLC method for determination of antihypertensive drugs and their degradation products in tablets: application to content uniformity and dissolution studies

A combination of candesartan cilexetil and hydrochlorothiazide in the tablet dosage form is developed by Takeda and recently approved by the United States Food and Drug Administration (USFDA) for the treatment of hypertension. The main objective of the current work was to optimize and develop a novel and robust stability-indicating reversed-phase ultra-performance liquid chromatography (RP-UPLC) method for simultaneous quantification of candesartan cilexetil and hydrochlorothiazide and their impurities in various tablet dosage forms and application to content uniformity and dissolution studies. The chromatographic condition is accomplished using a mobile-phase gradient system consisting of purified water-acetonitrile-glacial acetic acid (95:5:0.1, v/v) as mobile phase A and purified water-acetonitrile-glacial acetic acid (5:95:0.1, v/v) as mobile phase B at flow rate 0.4 ml/minute, wavelength 265 nm, injection volume 1.0 mu L, column oven temperature 30 degrees C, sample cooler temperature 15 degrees C, and ZORBAX Eclipse Plus RRHD C18 column (5 cm x 2.6 mm, 1.8 mu m). Calibration curves are achieved in the linearity range (1-240 mu g/mL) and (3-225 mu g/mL) with a correlation coefficient >= 0.9999 and a mean recovery percentage of 100.07 +/- 0.89 and 100.62 +/- 0.70 for candesartan cilexetil and hydrochlorothiazide, respectively. The suggested method is found to be selective as no overlapping showed from either solvent or placebo with the studied drugs and also purity threshold is greater than the purity angle under all forced degradation conditions. The current research of the developed UPLC method is validated as per the International Council for Harmonisation (ICH) guidelines and can be facilely applied in quality control or bioequivalence studies.

Automated summary

Takeda has developed a tablet dosage form combining candesartan cilexetil and hydrochlorothiazide for hypertension treatment, which has recently been approved by the USFDA. The objective of this study was to optimize and develop a stable reversed-phase ultra-performance liquid chromatography method for simultaneous quantification of candesartan cilexetil and hydrochlorothiazide in tablet dosage forms, and its application in content uniformity and dissolution studies.