Quantification of total and unbound tranexamic acid in human plasma by ultrafiltration liquid chromatography/tandem mass spectrometry: Application to pharmacokinetic analysis

Abstract The present work describes the development and validation of rapid, sensitive and accurate liquid chromatography method, coupled with tandem mass spectrometry detection, for quantification of tranexamic acid in human plasma using isotopically labeled internal standard (IS). A one-step plasma protein precipitation was performed with acetonitrile. UPLC BEH amide column was used for chromatographic separation. Tranexamic acid and IS were detected in multiple reaction monitoring in electrospray positive ionization. The method was linear over the concentration range of 0.8–200 mg/L. The intra- and inter-day precision values were below 11.5% and accuracy was better than 9.6%. Total analysis time was reduced to 6 min including sample preparation. The present method was successfully applied to pharmacokinetic pilot study in patients undergoing orthopedic surgery. Ultrafiltration allowed confirming the weak binding to plasma proteins and confirming that total plasma TXA concentration is measured by this assay.