Determination of Rivaroxaban in Rat Plasma by UHPLC-Q-Orbitrap HRMS and Its Application to A Pharmacokinetic Study.

Therapeutic drug monitoring is critical to decrease the incidence rate of bleeding and thrombosis for personalized treatment of rivaroxaban, especially for drug interaction treatment, renal dysfunction patients, elderly patients, cardiovascular patients, and so on. And, an accuracy analytical method is necessary to therapeutic drug monitoring. This study developed a ultra high performance liquid chromatography-tandem orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) method to accurately identify and quantify rivaroxaban in rat plasma. Isotope internal standard method was applied for accurate quantification. And rivaroxaban-d4 was selected as isotope internal standard substance. The m/z 436.07263 ([M+H]+ ) was selected as precursor ions and the m/z 144.95085, 231.11259 were selected as main product ions for rivaroxaban. The LLOQ of rivaroxaban in plasma was 0.01 mg/L. The intra- and inter-day precisions were ≤3.65 % and ≤8.16 %. And the recoveries were ranged from 87.4% to 95.2%. This analysis method was simple, low cost, and easy to operation and applied successfully to a pharmacokinetic study of rivaroxaban in rat plasma. This analysis method could be helpful to promote further research on the mechanism of rivaroxaban and drug interaction, which can avoid the false positives due to its high precision identification.