Development of a New Automated Assay for Measurement of the Oral Direct Factor Xa Inhibitor Edoxaban Plasma Concentration

Edoxaban is a reversible orally active factor Xa inhibitor approved in Japan for Venous ThromboEmbolism (VTE) prophylaxis in major orthopedic surgery and submitted for approval in multiple markets for Stroke Prevention in non-valvular Atrial Fibrillation (SPAF) and VTE treatment and recurrence prevention. Although routine monitoring is not required, determination of anti-Xa activity with results expressed in edoxaban plasma concentration may be helpful in some special clinical settings such as urgent invasive procedures or in cases of bleeding. We have developed a specific, automated, user-friendly assay for measuring plasma edoxaban-related anti-Xa activity using the STA® Liquid Anti-Xa with an edoxaban dedicated test set-up, along with specific edoxaban calibrator and control sets, namely STA® Edoxaban Calibrator and STA® Edoxaban Control, on the STA® line analyzers. These calibrator and control sets are freeze-dried in vitro edoxaban spiked citrated plasmas. Test results are expressed in ng/mL of edoxaban. Assay performances including Limit of Blank (LOB), Lower Limit of Detection (LLOD) both according to CLSI EP-17-A guideline, Lower Limit of Quantification (LLOQ), Upper Limit of Quantification (ULOQ) according to CLSI EP6-A guideline, with and without automated re-dilution of plasma sample, and within and between-run reproducibility have been determined. Anti-Xa assay results were compared to those obtained with Mass Spectrometry Liquid Chromatography (LC-MS) reference method to evaluate assay recovery. All study assays were performed using freeze-dried of frozen in vitro edoxaban-spiked citrated plasma samples. Main potential interferences, i.e ., hemoglobin, non-conjugated bilirubin, and lipemia, have been assessed. Assay performance results are summarized in Table I. In conclusion, the proposed edoxaban assay developed using STA® Liquid Anti-Xa reagent with a dedicated test set-up and specific STA® Edoxaban Calibrator and STA® Edoxaban Control sets allows an accurate, reproducible, automated, and user-friendly, edoxaban plasma concentration determination. Further studies are required to confirm assay performance in ex vivo samples. Disclosures Herve: Diagnostica Stago: Employment. Beaufils: Diagnostica Stago: Employment. Kochan: Daiichi Sankyo: Employment. He: Daiichi Sankyo: Employment. Depasse: Diagnostica Stago: Employment.