Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Biomed Chromatogr. 2022 May;36(5):e5306. doi: 10.1002/bmc.5306. Epub 2022 Feb 16.
Rivaroxaban is an oral anticoagulant directly inhibiting the activity of Factor Xa, which is widely used for the prophylaxis of thromboembolic disorders. Therapeutic drug monitoring (TDM) is required during therapy for individual dosage adjustment. This study aimed at developing a liquid chromatography/tandem mass spectrometry method that was suitable for rivaroxaban TDM in human plasma and urine and exploring the feasibility of urine drug monitoring in medical care. A 3 min run time of the LC-MS/MS methods was established by employing an Acquity UPLC BEH C (2.1 × 50 mm, 1.7 μm) column using gradient elution of 10 mmol/L ammonium acetate containing 0.1% formic acid-0.1% formic acid acetonitrile as a mobile phase at a flow rate of 0.4 ml/min with calibration ranges of 0.5-400 and 10-10,000 ng/ml for human plasma and urine, respectively. Rivaroxaban was detected on a triple quadrupole tandem mass spectrometer with an electrospray ionization source in positive ion mode. The methods showed good linearity within the calibration range. The precision and accuracy, matrix effect, extraction recovery and stability in both human matrices were all validated and meet the international guideline requirements. These validated methods were successfully applied to support the TDM of an aged patient receiving rivaroxaban for therapy.
利伐沙班是一种直接抑制 Xa 因子活性的口服抗凝剂，广泛用于预防血栓栓塞性疾病。治疗期间需要进行治疗药物监测（TDM），以进行个体化剂量调整。本研究旨在开发一种适用于人血浆和尿液中利伐沙班 TDM 的液相色谱/串联质谱法，并探讨在医疗保健中进行尿液药物监测的可行性。采用 Acquity UPLC BEH C（2.1×50mm，1.7μm）柱，以梯度洗脱方式，在 0.4ml/min 的流速下，使用含 10mmol/L 乙酸铵和 0.1%甲酸的 0.1%甲酸乙腈作为流动相，建立了 3 分钟运行时间的 LC-MS/MS 方法，校准范围分别为人血浆和尿液的 0.5-400 和 10-10,000ng/ml。利伐沙班在正离子模式下，采用电喷雾电离源，在三重四极杆串联质谱仪上进行检测。该方法在校准范围内具有良好的线性。在人基质中，精密度和准确度、基质效应、提取回收率和稳定性均经过验证，符合国际指南要求。这些经过验证的方法成功应用于支持接受利伐沙班治疗的老年患者的 TDM。
