Development and validation of a stability-indicating HPLC method for the simultaneous determination of losartan potassium, hydrochlorothiazide, and their degradation products

Losartan potassium was the first in a new class of potent angiotensin II receptor antagonists which are well-tolerated in the treatment of hypertension. Losartan potassium is the active ingredient in tablets COZAAR and is combined with diuretic co-active hydrochlorothiazide (HCTZ) in tablets HYZAAR for increased efficacy. Losartan potassium has one main impurity and two primary degradates. HCTZ has one major degradate as well as two common process impurities. Historically, separate methods have been used for the analysis of each active and their respective impurities and degradates. The ultimate goal of this work was to develop and validate a single high-performance liquid chromatography method selective for the eight main components of tablets HYZAAR. A single method was developed to afford simultaneous quantitation of actives and degradates for each of the two existing formulations. Each method is presented herein and demonstrated to be suitable for quantitation to 0.1% levels of all relevant degradates, as well as 100% levels of respective drug substances.