A simple and sensitive HILIC-based UHPLC-MS/MS method for quantifying of rivaroxaban in dried blood spots: Application in comparison with the plasma sample method

Abstract Rivaroxaban, indicated for the treatment of atrial fibrillation, deep vein thrombosis, pulmonary embolism, and coronary or peripheral artery disease, is one of the most frequently used direct oral anticoagulants. Therapeutic drug monitoring [TDM] is essential to minimize bleeding and thrombosis during personalized rivaroxaban treatment. An efficient and reliable analytical technique is required to quatify the rivaroxaban during its therapeutic indication. Dried blood spots (DBSs) sampling is a convenient bioanalytical method with minimal invasive blood drawing, long-term stability, and low shipment and storage costs. Therfore, DBS sampling technique is growing rapidly for TDM of drugs in medical care. This study developed an ultra high performance liquid chromatography–tandem mass spectrometry method of quantitating rivaroxaban in DBSs samples using the isotopic labeled analog (rivaroxaban-d4) as an internal standard (IS). Rivaroxaban and IS were separated on an Acquity HILIC column and eluted with a mobile-phase composition of acetonitrile and 20 mM ammonium acetate in the ratio of 95:5 at a flow rate of 0.3 mL/min. The precursor-to-product ion transitions of 436.03