Analysis of captopril and hydrochlorothiazide combination tablet formulations by liquid chromatography

A reverse-phase, high-performance liquid chromatographic (HPLC) procedure was developed for the simultaneous assay of captopril and hydrochlorothiazide in a combination tablet formulation. Gradient elution was used to quantify these two drugs, as well as the oxidized form of captopril, the disulfide. Tablets were extracted with methanol and, after centrifugation, were chromatographed. Initially, a methanol-0.05% aqueous phosphoric acid (25:75, v/v) solution was pumped at 2 mL/min into a phenyl column. After 8 min, the flow rate was increased to 4.5 mL/min and the methanol content of the mobile phase was increased to 45% to elute the disulfide. Detection was at 210 nm. Linearity and repeatability of all constituents were satisfactory. The hydrolytic degradation product of hydrochlorothiazide, 4-amino-6-chloro-1,3-benzene disulfonamide (also called the disulfonamide ), could be resolved in test solutions but was not visible in chromatograms of tablets carried through the gradient procedure even after storage at elevated temperatures for prolonged time periods prior to assay. The method can be automated.