LC–MS/MS determination of tranexamic acid in human plasma after phospholipid clean-up

Abstract

Tranexamic acid is a widely used antifibrinolytic drug but its pharmacology and pharmacokinetics remains poorly understood. Owing to the recent knowledge on phospholipid-induced matrix effects during human plasma analysis, our aim was to develop a liquid chromatography-mass spectrometry method for the quantitation of tranexamic acid after efficient sample clean-up. Sample preparation consisted in phospholipid removal and protein precipitation. Hydrophilic interaction liquid chromatography was used and the detection was achieved with multiple reaction monitoring. The method was validated according to the European Medicine Agency guideline in the range 1.0–1000.0μg/mL. The performance of the method was excellent with a precision in the range 1.2-3.0%, an accuracy between 88.4 and 96.6% and a coefficient of variation of the internal standard-normalized matrix factor below 6.7%. This method is suitable for the quantification of tranexamic acid in the wide range of concentrations observed during clinical studies, with all the advantages related to phospholipid removal.