Determination of edoxaban equivalent concentrations in human plasma by an automated anti-factor Xa chromogenic assay

Abstract Introduction This phase I, open-label, multiple-dose, two-treatment study assessed the relationship between edoxaban equivalent concentration derived from an anti-FXa assay with the summed concentration of edoxaban and its active metabolite, M-4, as assessed by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). This study also assessed the relationship between edoxaban plasma concentrations assessed by LC/MS/MS in sodium citrate and lithium heparin tubes. Materials and methods Healthy volunteers were randomized to receive once-daily edoxaban 60 mg or 90 mg for 5 days (15 participants per treatment group). Serial blood samples were collected for analysis by LC/MS/MS and by the anti-FXa assay. Edoxaban equivalent levels were assessed using a commercially available anti-FXa activity assay with an edoxaban-specific setup. Results and conclusions The day 5 concentration estimates were significantly correlated between the 2 assays ( P P P  = 0.0002). The GLSM ratio for edoxaban concentrations in sodium citrate vs lithium heparin tubes for 60-mg and 90-mg edoxaban doses were 82.8% (78.5–87.3) and 83.9% (79.1–89.0), respectively. In this study, an anti-FXa chromogenic assay with edoxaban-specific calibrators and controls demonstrated good accuracy in estimating edoxaban concentrations across a wide range of concentrations relative to LC/MS/MS at steady state following the administration of once-daily edoxaban for 5 days.