Xây dựng phương pháp định lượng đồng thời telmisartan và hydroclorothiazid trong huyết tương người bằng phương pháp LC-MS/MS

Abstract

A high and specific method using ultra performance liquid chromatography tandem mass spectrometry for simultaneous determination of telmisartan and hydrochlorothiazide in human plasma was developed. Telmisartan-d3 and hydrochlorothiazide-13C,d2 were utilized as internal standards. Analytes were extracted from plasma by protein precipitation using acetonitrile combined with sample freezing. Liquid chromatography was performed on Luna C18(2)-HST; (50 x 3 mm; 2.5µm) column with mixture of methanol and 5 mM ammonium acetate, with 0.1% acetic (80 : 20, tt/tt) as mobile phase at flow rate of 0.3 mL per minute. The method has a rapid analysis time and LLOQ value and standard curves were found to be linear in the wide range 1 to 1000 ng/mL for TEL and 1 to 400 ng/mL for HCT. The method’s precision and accurary are within acceptable limit. The validated method has been used successfully to determine telmisartan and hydrochlorothiazide concentrations in healthy adult volunteers and demonstrate its applicability to bioavailability/bioequivalence studies of telmisartan and hydrochlorothiazide combination preparations.