title: Development and validation of a LC-MS/MS method for determination of bivalirudin in human plasma: Application to a clinical pharmacokinetic study.
abstract: A simple, sensitive and rapid LC-MS/MS method has been developed and validated for the identification and quantification of bivalirudin in human plasma using nafarelin as the internal standard. Following protein precipitation with methanol, the analytes were separated on a C(18) column interfaced with a triple-quadrupole tandem mass spectrometer using positive electrospray ionization. Quantification of bivalirudin was conducted by multiple reaction monitoring (MRM) of the transitions of m/z 1091.4-->(356.4+227.4) for bivalirudin and m/z 662.4-->328.5 for IS. The lower limit of quantification was 1.25ng/ml, and the assay exhibited a linear range of 1.25-500ng/ml. The developed assay method was successfully applied to a pharmacokinetic (PK) study in healthy volunteers after intravenous administration of bivalirudin.
authors.affiliation: Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Pan
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiumei
authors.initials: X
authors.lastname: Gao
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D044466:Asian People; D002681:China; D002853:Chromatography, Liquid / Q000592:standards; D005260:Female; D006629:Hirudins / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074619:bivalirudin