摘要

A fast, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination of darusentan in rat plasma. Plasma samples were accomplished through protein precipitation. The separation was achieved by an Acquity UPLC BEH C18 column (2.1 x 50 mm, 1.7 mu m) with a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile. The total run time was 3 min and the elution of darusentan was at 1.51 min with 0.4 mL/min flow. The calibration curve was linear over the range of 5-2500 ng/mL (r(2) > 0.999) with a lower limit of quantitation (LLOQ) of 5 ng/mL. Mean recovery of darusentan in plasma was in the range of 81.9-82.6%. Intra-day and inter-day precision were both <7.71% and accuracy was from 2.95 to 7.28%. This method was successfully applied in a pharmacokinetic study after oral administration of 10.0 mg/kg darusentan in rats.