Determination of rivaroxaban--a novel, oral, direct Factor Xa inhibitor--in human plasma by high-performance liquid chromatography-tandem mass spectrometry.

A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method allowing the sensitive and specific quantification of rivaroxaban (BAY 59-7939), a Factor Xa inhibitor in advanced development for the prevention and treatment of thromboembolic disorders, in human plasma is described. After precipitation of plasma proteins with methanol containing the internal standard followed by centrifugation, the plasma supernatant was injected directly onto the HPLC-MS/MS system. Concentrations could be determined between 0.50 and 500 microg/L. Inter-assay precision was < or = 7.4% and inter-assay accuracy was between 96.3 and 102.9% throughout the entire working range. The method was applied successfully in several clinical studies, which allowed an accurate determination of rivaroxaban pharmacokinetics in human plasma.