Simultaneous determination of losartan and hydrochlorothiazide in combineddosage forms by first-derivative spectroscopy and high-performance thin-layer chromatography

Losartan (LST) is the first orally active nonpeptide angiotensin-II recepto r antagonist with an improved safety and tolerability profile. It is prescr ibed alone or in combination with hydrochlorothiazide (HCTZ) for the treatm ent of moderate-to-severe hypertension. This paper describes the developmen t of 2 methods that use different techniques, first-derivative spectroscopy and high-performance thin-layer chromatography (HPTLC), to determine LST a nd HCTZ in the presence of each other. LST and HCTZ in combined preparation s were quantitated by using the first-derivative responses at 271.6 nm for LST and 335.0 nm for HCTZ in spectra of their solutions in water. The linea rity ranges are 30-70 mug/mL for LST and 7.5-17.5 mug/mL for HCTZ with corr elation coefficients of 0.9998 and 0.9997, respectively. In the HPTLC metho d, a mobile phase of chloroform-methanol-acetone-formic acid (7.5 + 1.5 + 0 .5 + 0.03, v/v) and a prewashed Silica Gel G60 F-254 TLC plate as the stati onary phase were used to resolve LST and HCTZ in a mixture. Two well-separa ted and sharp peaks for LST and HCTZ were obtained at Rf values of 0.61 +/- 0.02 and 0.41 +/- 0.02, respectively. LST and HCTZ were quantitated at 254 .0 nm. The linearity ranges obtained for the HPTLC method are 400-1200 and 100-300 ng/spot with corresponding correlation coefficients of 0.9944 and 0 .9979, for LST and HCTZ, respectively. Both methods were validated, and the results were compared statistically. They were found to be accurate, speci fic, and reproducible. The methods were successfully applied to the estimat ion of LST and HCTZ in combined tablet formulations.