Pharmacokinetic Study of Zhebeirine in Mouse Blood by Ultra- Performance Liquid Chromatography/tandem Mass Spectrometry

Abstract

Introduction: In this study, a precise, rapid and accurate ultra-performance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS) method for the quantification of zhebeirine in mouse blood was developed, and pharmacokinetics of zhebeirine was studied for the first time after intravenous and oral administration. Methods: The mobile phase consisted of acetonitrile-0.1% formic acid, with a flow rate at 0.4 mL/m during 4 min run time. MRM modes of m/z 414.5→81.0 for zhebeirine and m/z 430.2→412.2 for 3- dehydroverticine (internal standard) were utilized to perform quantitative analysis. Protein in mouse blood was directly precipitated with acetonitrile for sample preparation. Results: The linear range was 1-3000 ng/mL with r>0.995, and LLOQ was 1 ng/mL. The intra-and inter-day precision of zhebeirine in mouse blood was less than 13%. The accuracy ranged from 91.2% to 112.5%, while the matrix effects were between 84.8% and 106.4%. Conclusion: The UPLC-MS/MS was successfully applied to the pharmacokinetic study on zhebeirine after intravenous and oral administration, and the bioavailability was determined to be 22.8%.