Abstract: A simple and sensitive high-performance liquid chromatography mass spectrometry (LC-MS) method for the simultaneous determination of irbesartan and hydrochlorothiazide in human plasma was developed and applied to a pharmacokinetic study. Acetaminophen was used as the internal standard (IS). Sample pretreatment using liquid-liquid extraction with ethyl acetate was used. The analysis was carried out on an Elite SinoChrom ODS-BP C18 column with a mobile phase composed of acetonitrile-water (35:65, v/v). Target ions were [M-H]^- m/z 427.25 for irbesartan, [M-H]^- m/z 295.95 for hydrochlorothiazide and [M-H]^- m/z 150.05 for the IS via an electrospray ionization (ESI) source. The intra- and inter-day precision (RSD%) was below 14.5% for irbesartan and hydrochlorothiazide, and the accuracy (RE%) was less than 1.9% and -2.0% for irbesartan and hydrochlorothiazide, respectively. The linear calibration curves were obtained in the concentration range of 10-5000 ng/mL (r>0.99) for irbesartan and 1-200 ng/mL (r>0.99) for hydrochlorothiazide with the lower limit of quantification (LLOQ) of 10 ng/mL and 1 ng/mL, respectively. The method was applied to a clinical pharmacokinetic study of a tablet containing irbesartan and hydrochlorothiazide in healthy Chinese volunteers after oral administration.

Key words: HPLC-MS, Irbesartan, Hydrochlorothiazide, Pharmacokinetics, Human plasma