A validated assay for the quantitative analysis of tranexamic acid in human serum by liquid chromatography coupled with electrospray ionization mass spectrometry

Background: Tranexamic acid is a synthetic lysine analog used for management of bleeding disorders. The objective of this study was first to develop a method for measurement of tranexamic acid in human serum using liquid chromatography coupled to ion-trap mass spectrometry (LC-MS/MS), and then to validate it throughout a wide range of concentrations allowing quantification in patients receiving tranexamic acid infusion during surgery. Methods: Serum samples (100 mu L) were subjected to protein precipitation with perchloric acid, and after pH adjustment, tranexamic acid and internal standard were separated on a C-18 column and isocratically eluted using a mobile phase constituted of formate buffer/acetonitrile (95:5, v/v). Tranexamic acid was ionized by electrospray in positive mode. Parent [M + H](+) ions were m/z 158.0 for tranexamic acid and m/z 144.0 for IS. The most intense product ion of tranexamic acid (m/z 122.7) and IS (m/z 126.0) were used for quantification. Results: The assay was accurate and precise over the range of 1.0 (lower limit of quantification) to 200.0 mu g/mL (upper limit of quantification), and has been successfully applied to study the clinical pharmacokinetics in two volunteers undergoing cardiac surgery. Conclusion: A reliable method for quantification of tranexamic acid for analysis in clinical studies was obtained. (C) 2010 Elsevier B.V. All rights reserved.