Apply hybrid (LBA)-LC-MS/MS approach to free Factor XI biomarker bioanalysis

China Bioanalysis Forum  2025 -- Factor XI (FXI) is the zymogen form of factor XIa, one of the enzymes involved in coagulation, that contributes to thrombin generation during blood coagulation by proteolytic activation of several coagulation factors, most notably Factor IX (FIX). Factor XI inhibitors as biotherapeutics directed against the soluble target (FXI), block FXI biological activities and offers the promise of hemostasis, sparing anticoagulation for the prevention and treatment of arterial and venous thromboembolic events. It also might reduce clotting risks without a corresponding increase in bleeding. Following dosing with Factor XI inhibition drug, Factor XI (FXI) is reduced compared with the initial baseline levels. Therapeutic efficacy is driven by free target suppression, which is the magnitude and duration of free Factor XI decreasing in vivo following drug treatment. Measurement of free Factor XI as a target engagement biomarker is required for the assessment of drug effect on the target.