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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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Research Article

An LC-MS/MS Method for the Pharmacokinetic and In Vitro Metabolism Studies of Praeruptorin A in Rat

Author(s): Zhuicheng Xu, An Kang*, Jinjun Shan, Mengmeng Song and Tong Xie

Volume 18, Issue 5, 2022

Published on: 27 August, 2021

Page: [520 - 527] Pages: 8

DOI: 10.2174/1573412917666210827103645

Price: $65

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Abstract

Objective: The study aims to investigate the pharmacokinetic profile of Praeruptorin A and khellactone and in vitro hydrolysis of praeruptorin A to khellactone in different biological samples.

Methods: A LC-MS/MS method was established. Analytes and internal standard (IS) were isolated using the protein precipitation method and then separated on a Thermo BDS Hypersil C18 (2.1 mm×50 mm, 2.4μm) column using a mobile phase consisting of 0.05% formic acid solution and acetonitrile. Samples were analyzed in positive electrospray-ionization (ESI) mode using multiple reaction monitoring (MRM).

Results: The calibration plots gave desirable linearity (r2>0.99) in the concentration range from 0.99-990.0 and 2.0-2000.0 ng/mL for Praeruptorin A and khellactone, respectively. In addition, the LOQs of these analytes were sufficient for vivo pharmacokinetic study and vitro hydrolysis study of Praeruptorin A. The intra-batch and inter-batch precision were all within 14.05%, and the accuracy was between 89.39% and 109.50%. The extraction efficiency of PA and khellactone ranged from 76.35 ~ 89.58%. The matrix effects of analytes and the IS were between 89.67% ~ 105.26%.

Conclusion: The liver CYPs mediated by the metabolism of PA may contribute to the systemic exposure of its active metabolite, khellactone, in rats.

Keywords: Praeruptorin A, liquid chromatography-tandem mass spectrometry, pharmacokinetics, hydrolysis metabolism, khellactone, P450.

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