Validated stability-indicating HPLC-DAD method of analysis for the antihypertensive triple mixture of amlodipine besylate, valsartan and hydrochlorothiazide in their tablets

Abstract

A simple and selective HPLC-DAD stability indicating method was developed for the simultaneous determination of the three antihypertensive drugs amlodipine besylate (AML), valsartan (VAL) and hydrochlorothiazide (HCT) in their combined formulation. Effective chromatographic separation was achieved using Zorbax SB-C8 column (4.6 × 250 mm, 5 μm ps) with gradient elution of the mobile phase composed of 0.025 M phosphoric acid and acetonitrile at a flow rate of 1 mL/min. The multiple wavelength detector was set at 238 nm for measurement of AML and 225 nm for both VAL and HCT. Quantification was based on measuring the peak areas. The three compounds were resolved with retention times of 4.9, 6.4 and 8.3 min for HCT, AML and VAL respectively. Analytical performance of the proposed HPLC procedure was statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. The linearity ranges were 5–200, 5–200 and 10–200 μg/mL for AML, VAL and HCT respectively with correlation coefficients >0.9993. The three drugs were subjected to stress conditions of acidic and alkaline hydrolysis, oxidation, photolysis and thermal degradation. The proposed method proved to be stability-indicating by resolution of the analytes from their forced-degradation products. The validated HPLC method was applied to the analysis of the cited antihypertensive drugs in their combined pharmaceutical tablets (Exforge HCT). The proposed method made use of DAD as a tool for peak identity and purity confirmation.

Keywords

• Amlodipine besylate
• Valsartan
• Hydrochlorothiazide
• Stability-indicating HPLC-DAD
• Stress degradation
• Pharmaceutical tablets