title: 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 0.8-200mg/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 6min 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.
authors.affiliation: Laboratory of Pharmacology and Toxicology, University Hospital, F-42055 Saint-Etienne, France; Thrombosis Research Group (EA 3065), University Jean Monnet, F-42023 Saint-Etienne, France. Electronic address: xavier.delavenne@chu-st-etienne.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Delavenne
authors.affiliation: Laboratory of Pharmacology and Toxicology, University Hospital, F-42055 Saint-Etienne, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Montbel
authors.affiliation: Laboratory of Pharmacology and Toxicology, University Hospital, F-42055 Saint-Etienne, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Hodin
authors.affiliation: Thrombosis Research Group (EA 3065), University Jean Monnet, F-42023 Saint-Etienne, France; Department of Anesthesiology and Intensive Care, University Hospital, F-42055 Saint-Etienne, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Zufferey
authors.affiliation: Laboratory of Pharmacology and Toxicology, University Hospital, F-42055 Saint-Etienne, France; Thrombosis Research Group (EA 3065), University Jean Monnet, F-42023 Saint-Etienne, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Basset
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D010949:Plasma / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014148:Tranexamic Acid / Q000737:chemistry* / Q000493:pharmacokinetics*; D014462:Ultrafiltration / Q000379:methods*
chemical_list: D014148:Tranexamic Acid
keywords: Liquid chromatography; Tandem mass spectrometry; Tranexamic acid; Ultrafiltration; antifibrinolytic