抽象的

Stability-Indicating HPLC Method for Simultaneous Determination of Metoprolol Succinate and Hydrochlorothiazide in Combination Drug Products

Vijaya P. Godse, Ashok V. Bhosale, Yogesh S. Bafana and Dhanaraj D. Borkar

A stability-indicating HPLC method has been developed and subsequently validated for the simultaneous determination of metoprolol succinate and hydrochlorothiazide in commercial tablets. The proposed HPLC method utilizes Kya Tech corporation® HiQ sil C18 W (250 mm × 4.6 mm i. d., 10 μm) and mobile phase consisting of acetonitrile-10 mM potassium dihydrogen phosphate pH 3.0 (17 : 83, v/v) for 3 min, then changed to 55 : 45 (v/v) for next 20 min and finally equilibrated back to 17 : 83 (v/v) from 20 to 25 min. at a flow rate of 1.0 mL min–1. Quantitation was achieved with UV detection at 270 nm and 224 nm for metoprolol succinate and hydrochlorothiazide, respectively, based on peak area with linear calibration curves at concentration ranges 100-1000 μg mL–1 for metoprolol succinate and 50-500 μg mL–1 for hydrochlorothiazide (R2 > 0.999 for both drugs). The method was validated in terms of accuracy, precision, linearity and robustness. This method has been successively applied to pharmaceutical formulation and no interference from the tablet excipients was found. Metoprolol succinate, hydrochlorothiazide and their combination drug product were exposed to acid, base, neutral hydrolysis; oxidation, dry heat, photolytic stress conditions and the stressed samples were analyzed by the proposed method. As the proposed method could effectively separate the drug from its degradation products, it can be employed as stability-indicating method for the determination of instability of these drugs in bulk and commercial products.