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A rapid and sensitive LC-MS/MS assay for the determination of berbamine in rat plasma with application to preclinical pharmacokinetic study.

Abstract
Berbamine (BBM), a natural compound from Chinese herb Berberis amurensis, has recently received a great deal of attention due to its anti-leukemia activity. In this study, a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of BBM in rat plasma was developed for the first time. Caffeine was used as an internal standard. Chromatographic separation was performed on an ODS column with gradient elution using methanol-1% formic acid as mobile phase at a flow rate of 0.3mL/min. Quantification was through tandem mass spectrometry with positive electrospray ionization (ESI) and multiple reaction monitoring (MRM) at m/z 305.2→566.3 and 195.1→138.0 for BBM and IS, respectively. The lower limit of quantification was 1ng/mL with a linear range of 1-1000ng/mL. The intra- and inter-day assay precision (RSD) ranged from 2.0-6.4% to 2.5-5.5%, respectively, and the intra- and inter-day assay accuracy (RE) was between -5.8-6.0% and -6.5-1.4%, respectively. The validated method was successfully applied to the preclinical pharmacokinetic studies of BBM in rats. The elimination half-lives (t1/2) were (472.4±66.1), (509.6±97.0) and (486.2±94.6) min after single intravenous administration of 2, 4 and 8mg/kg BBM, respectively. The area under the plasma concentration versus time curve (AUC0-24h) and initial plasma concentration (C0) were linearly related to dose.
AuthorsQingwang Liu, Junsong Wang, Lei Yang, Yuanwei Jia, Lingyi Kong
JournalJournal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 929 Pg. 70-5 (Jun 15 2013) ISSN: 1873-376X [Electronic] Netherlands
PMID23660248 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Benzylisoquinolines
  • berbamine
Topics
  • Animals
  • Benzylisoquinolines (blood, pharmacokinetics)
  • Chromatography, Liquid (methods)
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Tandem Mass Spectrometry (methods)

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