Quantitation of bivalirudin, a novel anticoagulant peptide, in human plasma by LC-MS/MS： Method development, validation and application to pharmacokinetics

A rapid and sensitive method based on liquid chromatographtandem mass spectrometry （LC-MS/MS） for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and reextracted with dichlorom...

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Bibliographic Details
Published in:Journal of pharmaceutical analysis 2013-02, Vol.3 (1), p.1-8
Main Authors: Li, Xiao-Jiao, Sun, Yan-Tong, Yin, Lei, Zhang, Xue-Ju, Yang, Yan, Paul Fawcett, J., Cui, Yi-Min, Gu, Jing-Kai
Format: Article
Language:English
Subjects:
Anticoagulant
Bivalirudin
Human plasma
LC-MS
LC–MS/MS
Pharmacokinetics
S方法
人体血浆
应用
开发
抗凝血剂
药代动力学
验证
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Summary:A rapid and sensitive method based on liquid chromatographtandem mass spectrometry （LC-MS/MS） for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and reextracted with dichloromethane, after which the analyte and triptorelin as an internal standard （IS） were separated on a 300SB-Cl8 column （150 mm x 4.6 mm i.d., 5 gm particle size） using 0.1% formic acid：methanol （45：55, v/v） as mobile phase. The triple-quadrupole mass spectrometer, equipped with electrospray ionization （ESI） interface, was operated in the positive ion mode, and the multiplereaction monitoring （MRM） transitions of bivalirudin and IS were at m/z 1091.0-650.4 and m/z656.5 - 249.3, respectively. The lower limit of quantification （LLOQ） was 1 ng/mL for 100 ng/mL plasma sample and the assay was linear over the concentration range 1 1000 ng/mL. The accuracy was within a range from -0.4% to 0.5% in terms of relative error （RE） and the intra- and inter-day precisions in terms of relative standard deviation （RSD） were 〈2.92 and 〈 3.36, respectively. The method was successfully applied to a pharmacokinetic study involving intravenous administration of bivalirudin （0.5 mg/kg） to Chinese volunteers.
ISSN:2095-1779
2214-0883
DOI:10.1016/j.jpha.2012.10.006