Novel spectrophotometric methods for simultaneous determination of Amlodipine, Valsartan and Hydrochlorothiazide in their ternary mixture.

This work represents a comparative study of two smart spectrophotometric techniques namely; successive resolution and progressive resolution for the simultaneous determination of ternary mixtures of Amlodipine (AML), Hydrochlorothiazide (HCT) and Valsartan (VAL) without prior separation steps. These techniques consist of several consecutive steps utilizing zero and/or ratio and/or derivative spectra. By applying successive spectrum subtraction coupled with constant multiplication method, the proposed drugs were obtained in their zero order absorption spectra and determined at their maxima 237.6 nm, 270.5 nm and 250 nm for AML, HCT and VAL, respectively; while by applying successive derivative subtraction they were obtained in their first derivative spectra and determined at P230.8-246, P261.4-278.2, P233.7-246.8 for AML, HCT and VAL respectively. While in the progressive resolution, the concentrations of the components were determined progressively from the same zero order absorption spectrum using absorbance subtraction coupled with absorptivity factor methods or from the same ratio spectrum using only one divisor via amplitude modulation method can be used for the determination of ternary mixtures using only one divisor where the concentrations of the components are determined progressively. The proposed methods were checked using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical formulation containing the cited drugs. Moreover comparative study between spectrum addition technique as a novel enrichment technique and a well established one namely spiking technique was adopted for the analysis of pharmaceutical formulations containing low concentration of AML. The methods were validated as per ICH guidelines where accuracy, precision and specificity were found to be within their acceptable limits. The results obtained from the proposed methods were statistically compared with the reported one where no significant difference was observed.