UBFC, EA3920, Univ Bourgogne Franche-Comte, F- 25000 Besancon, France; CHU Besancon, Service de Pharmacologie Clinique et Toxicologie, 25000 Besancon, France.
CHU Besancon, Service de Pharmacologie Clinique et Toxicologie, 25000 Besancon, France.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Nov 15;1100-1101:43-49. doi: 10.1016/j.jchromb.2018.09.026. Epub 2018 Sep 27.
Direct Oral Anticoagulants (DOACs) available for the treatment and prevention of thromboembolic diseases include dabigatran, a direct thrombin (IIa) inhibitor, and apixaban, edoxaban and rivaroxaban, which are direct inhibitors of Stuart factor (Xa). DOACs have a different pharmacokinetic and pharmacodynamics profiles, with less probable drug-drug interactions than vitamin K antagonists. They do not require systematic therapeutic monitoring except in specific clinical situations such as emergency procedures or drug non-compliance. Furthermore, anticoagulant effects of DOACs could be impacted by renal impairment, drug-drug interactions, food interactions, or pharmacogenetic variability. In this context, we developed a method for simultaneous determination of dabigatran, rivaroxaban and apixaban in human plasma using high performance liquid chromatography coupled with a mass spectrometry assay and applied it to 26 patient samples. Our method presents a total run time of 5 min and extends from 25 to 1000 μg/L for apixaban and dabigatran; and from 5 to 1000 μg/L for rivaroxaban. Intra- and inter-assay accuracy were between -22.3 and 25.4%; and - 23.7 and 3.8%, respectively. Precision at low and high concentrations were below 17.5%. Frozen samples were stable up to 3 months. No significant cross-contamination was observed. In conclusion, our assay can be used during clinical studies and in daily routine practice for the management of specific clinical situations at reasonable cost.
直接口服抗凝剂（DOACs）可用于治疗和预防血栓栓塞性疾病，包括达比加群，一种直接凝血酶（IIa）抑制剂，以及阿哌沙班、依度沙班和利伐沙班，它们是 Stuart 因子（Xa）的直接抑制剂。DOACs 具有不同的药代动力学和药效学特征，与维生素 K 拮抗剂相比，药物相互作用的可能性更小。除了在紧急情况下或药物不依从的情况下，它们不需要系统的治疗监测。此外，DOACs 的抗凝效果可能受到肾功能损害、药物相互作用、食物相互作用或药物遗传学变异性的影响。在这种情况下，我们开发了一种同时测定人血浆中达比加群、利伐沙班和阿哌沙班的方法，该方法采用高效液相色谱-质谱联用技术，并将其应用于 26 个患者样本。我们的方法总运行时间为 5 分钟，阿哌沙班和达比加群的检测范围为 25-1000μg/L；利伐沙班的检测范围为 5-1000μg/L。内、日间准确度在-22.3%至 25.4%之间；-23.7%至 3.8%。低浓度和高浓度的精密度均低于 17.5%。冷冻样本在 3 个月内稳定。未观察到明显的交叉污染。总之，该检测方法可在临床研究中以及在日常实践中用于管理特定的临床情况，成本合理。
