RESUMEN
A simple, precise and stability-indicating HPLC method was developed and validated for the simultaneous determination of bisoprolol fumarate and hydrochlorothiazide in pharmaceutical dosage form. The method involves the use of easily available inexpensive laboratory reagents. The separation was achieved on an Inertsil ODS 3V (25cmx4.6mm) 5microm column with isocratic flow. The mobile phase at a flow rate of 1.0mLmin(-1), consisted of 0.1M potassium dihydrogen phosphate buffer and acetonitrile (70:30, v/v). The UV detection was carried out at 228nm. A linear response was observed over the concentration range 2.5-50microgmL(-1) of bisoprolol fumarate and the concentration range 6.25-125microgmL(-1) of hydrochlorothiazide. Limit of detection and limit of quantitation for bisoprolol fumarate were 0.01 and 0.03microgmL(-1), respectively and for hydrochlorothiazide were 0.01 and 0.05microgmL(-1), respectively. The method was successfully validated in accordance to ICH guidelines acceptance criteria for specificity, linearity, accuracy, precision, robustness, ruggedness and system suitability. Individual drugs (bisoprolol fumarate and hydrochlorothiazide), their combinations and the tablets were exposed to thermal, photolytic, hydrolytic and oxidative stress conditions. The resultant stressed samples were analyzed by the proposed method. The method gave high resolution among the degradation products and the analytes. The peak purity of analyte peaks in the stressed samples was confirmed by photodiode array detector. The method was used for accelerated stability study on marketed and in-house formulations. The analysis concluded that the method was selective for simultaneous estimation of bisoprolol fumarate and hydrochlorothiazide and was stability-indicating.