- Journal
- JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
- Année
- 2018
- Volume
- 1100
- Pages
- 43-49
- Mois
- NOV 15
- DOI
- 10.1016/j.jchromb.2018.09.026
Abstract
Direct Oral Anticoagulants (DOACs) available for the treatment and prevention of thromboembolic diseases include dabigatran, a direct thrombin (Ha) 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 mu g/L for apixaban and dabigatran; and from 5 to 1000 mu g/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.