Laboratory monitoring of rivaroxaban in Chinese patients with deep venous thrombosis: a preliminary study.

Background: Rivaroxaban, a novel oral anticoagulant drug, is widely used in clinical practice. There is no standardized laboratory monitoring for rivaroxaban, and its plasma concentration in Chinese patients with deep vein thrombosis is unclear. The rivaroxaban concentrations in human plasma and determine the steady-state concentration of rivaroxaban in patients with deep vein thrombosis are needed.

Methods: An ultra-high-performance liquid chromatography with mass spectrometric detection method was developed. Chromatographic separation was performed on a Waters BEH C18 column with isocratic elution using a mobile phase composed of acetonitrile and water. Quantitation of the analytes was performed using positive ionization mode and mass transitions of m/z 437.3 → m/z 145.0 and m/z 440.1 → m/z 145.0 for rivaroxaban and the internal standard, respectively. Blood samples were collected at 0 h and 2 h after patients took rivaroxaban for 7 days or more.

Results: The method was validated over the concentration range of 0.5 ~ 400 ng•mL with a very low limit of quantification of 0.5 ng·mL, and the intra- and inter-day precision (RSD%) were < 15%. The range of the steady state concentration in patients that took 15 mg rivaroxaban twice daily, 10 mg twice daily, 20 mg once daily, 15 mg once daily, and 10 mg once daily were 168.5 ~ 280.1 ng•mL, 74.2 ~ 271.4 ng•mL, 25.7 ~ 306.8 ng•mL, 24.5 ~ 306.4 ng•mL, and 15.4 ~ 229.2 ng•mL, respectively.

Conclusions: The plasma rivaroxaban concentration in patients who took 10 mg rivaroxaban twice daily fluctuated less than that in patients who took 20 mg rivaroxaban once daily. The plasma concentration can be used for therapeutic drug monitoring for rivaroxaban.