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http://dx.doi.org/10.12793/jkscpt.2013.21.2.166

Validation of LC-MS/MS Method for Determination of Bivalirudin in Human Plasma: Application to a Pharmacokinetic Study  

Kim, Yo Han (Department of Clinical Pharmacology and Therapeutics, Asan Medical Center)
Park, Hyun Jeong (Clinical Trial Center, Asan Medical Center)
Choi, Hee Youn (Department of Clinical Pharmacology and Therapeutics, Asan Medical Center)
Lim, Hyeong-Seok (Department of Clinical Pharmacology and Therapeutics, Asan Medical Center)
Bae, Kyun-Seop (Department of Clinical Pharmacology and Therapeutics, Asan Medical Center)
Publication Information
Journal of Korean Society for Clinical Pharmacology and Therapeutics / v.21, no.2, 2013 , pp. 166-173 More about this Journal
Abstract
Background: Bivalirudin is a direct thrombin inhibitor for patients with unstable angina undergoing percutaneous coronary intervention. Methods: A sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of bivalirudin, in human plasma using nafarelin as internal standard (IS). Chromatographic separation was performed using a Shiseido MG3 mm column ($2.0{\times}50$ mm) with a gradient mobile phase consisting of water and acetonitrile containing 0.1 % formic acid at a flow rate of 0.4 mL/min, and total run time was within 5 min. Detection and quantification was performed by the mass spectrometer using a multiple reaction-monitoring mode at m/z $1091.0{\rightarrow}650.3$ for bivalirudin, and m/z $662.1{\rightarrow}249.3$ for IS. Results: The assay was linear over a concentration range of 10 - 10000 ng/mL with a lower limit of quantification of 10 ng/mL in human plasma. Conclusion: This method was successfully applied for pharmacokinetics study after intravenous administration of bivalirudin to healthy Korean male volunteers.
Keywords
Bivalirudin; Liquid chromatography; Pharmacokinetics;
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