30. Measurement of Plasma Tranexamic Acid Levels in Coronary Artery Bypass Graft Patients Using a Novel Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry Assay

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Charbel Abou-Diwan Emory University School of Medicine

*Charbel Abou-Diwan, #Kenichi Tanaka, *Ross J. Molinaro *Department of Pathology and Laboratory Medicine and #Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322

Tranexamic acid is a synthetic derivative of the amino acid lysine that possesses potent antifibrinlolytic activity. It has been used to decrease post-operative blood loss in patients with primary coronary artery bypass grafting (CABG). Despite the available literature describing the safety and effectiveness of tranexamic acid administration in patients undergoing CABG, some patients suffer from side effects such as seizures of unknown causes. Patients undergoing surgeries receive a bolus dose of tranexamic acid. There is a paucity of data examining the pharmacokinetics of tranexamic acid levels pre- and post-surgery. Therefore, we have developed a novel method for the identification and quantitation of tranexamic acid in human plasma using ultra performance liquid chromatogrpahy-tandem mass spectrometry for use in pharmacokinetic studies of tranexamic acid. After the addition of deuterated ursodeoxycholic acid (UDCA-D4) as the internal standard, tranexamic acid is isolated from plasma by methanol extraction. Gradient chromatographic separations are performed on a Waters ACQUITY UPLC BEH C18 column using an ammonium acetate/formic acid mobile phase. Tranexamic acid demonstrated a reproducible elution time of 1.56 minutes while UDCA D4, consistently eluted from the column at 2.15 minutes. Both tranexamic acid, and UDCA D4 were monitored in the MRM mode (Waters Quattro Micro) using the hydrogen adduct mass transitions. Primary (158.2>95.2, tranexamic acid) and secondary (158.2>123.0, tranexamic acid) ion ratios were calculated as an additional check of compound specificity. Acceptable precision was demonstrated by both within-run and between-run experiments using drug-free plasma spiked with known low, medium, and high concentrations of tranexamic acid. Ion suppression was tested by sample addition and infusion assays. The tranexamic acid standard curve for plasma displayed a wide analytical measuring range with linearity up to 30 µg/mL and a limit of quantitation at 50 ng/mL. The corresponding range is suitable for measurement of plasma levels of tranexamic acid in our patient population after administration of a bolus dose of tranexamic acid and can be used to determine the optimum dosage in patients undergoing CABG at Emory University Hospital.

Email: caboudi@emory.edu

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