Plasma and cerebral spinal fluid tranexamic acid quantitation in cardiopulmonary bypass patients

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2011-03, Vol.879 (7), p.553-556
• Main Authors: Abou-Diwan, Charbel, Sniecinski, Roman M., Szlam, Fania, Ritchie, James C., Rhea, Jeanne M., Tanaka, Kenichi A., Molinaro, Ross J.
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Antifibrinolytic Agents - blood; Antifibrinolytic Agents - cerebrospinal fluid; Antifibrinolytic Agents - pharmacokinetics; Biological and medical sciences; blood plasma; Bypasses; Cardiopulmonary Bypass; Cardiopulmonary bypass surgery; Cerebral spinal fluid; cerebrospinal fluid; Chromatography; Chromatography, High Pressure Liquid; Fluid dynamics; Fluid flow; Fluids; formic acid; Fundamental and applied biological sciences. Psychology; General pharmacology; Hemoglobins - analysis; Humans; Ionization; Liquid chromatography; Mass spectrometry; Medical sciences; methanol; Methyl alcohol; monitoring; Patients; Pharmacology. Drug treatments; Plasma; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; surgery; Tandem Mass Spectrometry; Tranexamic acid; Tranexamic Acid - blood; Tranexamic Acid - cerebrospinal fluid; Tranexamic Acid - pharmacokinetics; ultra-performance liquid chromatography
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2011.01.005

A method for the determination of tranexamic acid (TXA) in human plasma and cerebral spinal fluid (CSF) was developed. Analyses were performed by ultra performance liquid chromatography with tandem mass spectrometry detection (UPLC–MS/MS) using ɛ-aminocaproic acid (ACA) as an internal standard. TXA and ACA were extracted from a 50 μL sample of plasma or CSF using a methanol protein crash protocol, and chromatographic separation was performed on an ACQUITY™ TQD mass spectrometer using a UPLC C18 BEH 1.7 μm column with a water and methanol gradient containing 0.1% formic acid. The detection and quantitation was performed by positive ion electrospray ionization using the multiple reaction monitoring (MRM) mode. The method was linear over the concentration range of 0.1–10.0 μg/mL, with lower limit of quantitation of 0.1 μg/mL for TXA. The intra- and inter-assay precision was less than 12% and 13% respectively at the plasma and CSF TXA concentrations tested. The present method provides a relatively simple and sensitive assay with short turn-around-time. The method has been successfully applied to assess the plasma and CSF concentrations of tranexamic acid achieved with only one dosing regimen of tranexamic acid in patients undergoing cardiopulmonary bypass surgery (CPB).