This presentation summarizes the development and validation of a stability-indicating HPLC method for the simultaneous determination of losartan potassium, hydrochlorothiazide, and their degradation products from tablet formulations. A gradient elution method using a C8 column and mobile phase of phosphate buffer and acetonitrile was developed and optimized. The method was validated per ICH guidelines and demonstrated selectivity, accuracy, precision, ruggedness and robustness for quantifying losartan, hydrochlorothiazide and up to two degradation products at levels as low as 0.1% from a single sample preparation. The method provides advantages over separate analyses in terms of time, solvent and sample requirements.