Total error-based validation including the experimental design-based robustness evaluation of a stability-indicating method for the simultaneous quantification of hydrochlorothiazide and valsartan in tablet formulations

Abstract

Summary.A gradient reversed phase high-performance liquid chromatography (RP-HPLC) method with ultraviolet (UV) detection to analyze hydrochlorothiazide (HCT) and valsartan (VS) simultaneously in a tablet formulation during forced degradation studies was developed. This method was validated using a novel approach, namely, the accuracy profile or total errors approach. The robustness of the method was evaluated using a Plackett-Burman design for eight factors. The algorithm of Dong was applied to determine the significant factor effects. The validation results showed that the method is precise (RSD: 1.14% for HCT and 0.43% for VS) and accurate (mean recovery: 99.90% for HCT and 99.98% for VS). On the other hand, the results of the robustness study showed that the type of column was the important factor which affects a number of responses, namely, the asymmetry factor (AF), retention time (RT), and resolution (RS). However, the assay results were not affected; therefore, the method can be considered robust. Finally, the method was applied to study the stability of HCT and VS under forced conditions. Significant results were obtained with basic hydrolysis, oxidation, and thermal stress, while the accelerated and acidic conditions did not affect the stability of HCT or VS.