Monitoring of Impurity Level of Valsartan and Hydrochlorothiazide Employing an RP–HPLC Gradient Mode

Abstract

The multi‐component preparation Co–Diovan® is indicated for the hypertension treatment in patients whose blood pressure is not adequately controlled by monotherapy. Its active ingredients are valsartan and hydrochlorothiazide. The reversed–phase high performance liquid chromatographic method (RP–HPLC) for the determination of valsartan and hydrochlorothiazide, as well as their impurities level, was developed and described in this paper. As the investigated substances were structurally different with extremely different lipophilicity and polarity, isocratic elution was not possible, so an optimal gradient mode was settled on. The chromatograms were recorded using the Agilent 1100 Series chromatographic system with DAD detector. Separations were performed on a Hypersil 120–5 ODS column (250 mm×4.6 mm; 5 µm particle size) at 25°C column temperature. The gradient high performance liquid chromatographic system was developed, and the following mobile phases were used: A) mixture acetonitrile–water (10:90 V/V); pH of the mobile phase was adjusted to 2.5 with 85% orthophosphoric acid, and B) mixture acetonitrile–water (90:10 V/V); pH of the mobile phase was adjusted to 2.5 with 85% orthophosphoric acid. Injection volume was 50 µL, flow rate 1 mL min−1 and UV detection was performed at 256 nm. Methyl parahydroxybenzoate was used as an internal standard and acetonitrile–water (40:60 V/V) as a solvent. Afterwards, the developed method was subjected to the method validation. The investigated validation parameters (selectivity, linearity, precision, accuracy, LOQ, and LOD) proved the suitability of the method for the simultaneous determination of valsartan, hydrochlorothiazide, and their impurities in appropriate tablets.