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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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General Research Article

Integrated UPLC-MS/MS and UHPLC-Q-orbitrap HRMS Analysis to Reveal Pharmacokinetics and Metabolism of Five Terpenoids from Alpiniae oxyphyllae Fructus in Rats

Author(s): Lihua Zuo, Jia Li, Lianping Xue, Qingquan Jia, Zhuolun Li, Mengya Zhang, Mengfan Zhao, Mengli Wang, Jian Kang, Shuzhang Du* and Zhi Sun*

Volume 22, Issue 1, 2021

Published on: 17 December, 2020

Page: [70 - 82] Pages: 13

DOI: 10.2174/1389200221666201217154219

Price: $65

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Abstract

Background: Alpiniae oxyphyllae Fructus (AOF), a traditional Chinese medicine (TCM), is widely used in the treatment of urinary, gastrointestinal and neurologic diseases in China. Although terpenoids are the main active ingredients of AOF, there are few researches on their pharmacokinetics and metabolism.

Methods: In this study, a sensitive, rapid, accurate and novel ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to evaluate the pharmacokinetic behavior of five terpenoids (oxyphyllenodiol B, (4S*,5E,10R*)-7-oxo-tri-nor-eudesm-5-en-4β-ol, 7-epi-teucrenone, (+)- (4R,5S,7R)-13-hydroxynootkatone, (E)-labda-12,14-dien-15(16)-olide-17-oic acid) in rats after oral administration of AOF extracts. 27 metabolic metabolites of the five terpenoids were identified by ultra high performance liquid chromatography -Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) based on precise mass and fragment ions.

Results: The established pharmacokinetic analysis method showed good linearity over a wide concentration range, and the lower quantitative limit (LLOQ) ranged from 0.97 to 4.25 ng/mL. Other validation parameters were within the acceptable range. In addition, 27 metabolites were identified in plasma, urine and feces samples, and the metabolic pathways of five terpenoids were mainly focused on glucoside conjugation, dehydration, desaturation and glycine conjugation.

Conclusion: This is the first study on the pharmacokinetics and metabolism of five terpenoids in AOF, illuminating the disposal process of terpenoids in vivo. It was expected that the results of this study would provide some references for the apprehension of the action mechanism and the further pharmacological study of five terpenoids in AOF.

Keywords: Alpiniae oxyphyllae Fructus, terpenoids, pharmacokinetics, metabolite profiling, UPLC-MS/MS, UHPLC-Q-orbitrap HRMS.

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