Study on Plasma Concentration and Pharmacokinetics of Darusentan in Rat Plasma by UPLC-MS/MS

OBJECTIVE To develop a rapid, highly sensitive and selective UPLC-MS/MS for the determination of darusentan in rat plasma. METHODS Plasma samples were processed by protein precipitation. The separation was achieved by a gradient mobile phase, consisting of an aqueous solution of 0.1% formic acid and acetonitrile using an Acquity UPLC BEH C₁₈ column (2.1 mm×50 mm, 1.7 μm). The flow rate was 0.4 mL·min^-1. ESI⁺ was used to detect. The scanning mode was MRM. RESULTS The standard curve was linear over the range of 0.01-2.5 μg·mL^-1(R²>0.999 6) with a LLOQ of 0.01 μg·mL^-1. The average recovery of darusentan in plasma was 87.613%-97.115%. The RSD of intra-and inter-assay precision andaccuracy were <7.71%. The RSD of matrix effect was <9.34%. CONCLUSION This method is successfully applied in pharmacokinetic study after oral administration of 10.0 mg·kg^-1 darusentan in rats.