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Comparative metabolism and stability of andrographolide in liver microsomes from humans, dogs and rats using ultra-performance liquid chromatography coupled with triple-quadrupole and Fourier transfor
Zhao, Hai-Yu1; Hu, Hao2; Wang, Yi-Tao1
2013-07-30
Source PublicationRAPID COMMUNICATIONS IN MASS SPECTROMETRY
ISSN0951-4198
Volume27Issue:12Pages:1385-1392
Abstract

RATIONALE Andrographolide (AP) is a major active anti-inflammatory compound extracted from Andrographis paniculata Nees. The metabolism stability ofAP is one of the key factors for its further development as a new drug candidate. In order to clarify the biotransformation of AP among species, a comparativeinvestigation of its in vitro metabolic pathways in human, dog and rat liver microsomes was carried out. METHODS In the present study, the in vitro metabolic profiles of AP using pooled human (HLMs), dog (DLMs) and rat (RLMs) liver microsomes were studied. The in vitro biotransformation including phase I and phase II incubation systems and metabolic stabilities of AP were studied for the first time. Ultra-performance liquid chromatography (UPLC) coupled with Fourier transform ion cyclotron resonance (FTICR) and tandem mass spectrometry (MS/MS) was used for identification of metabolites and quantification of AP. RESULTS Eight phase I and five phase II metabolites resulted from dehydration, deoxygenation, hydrogenation and glucuronidation were tentatively identified by accurate mass measurement and MS/MS fragmentation behavior. A dehydration reaction was detected in all these incubation systems. Deoxy-AP and the related glucuronide metabolites were observed in HLMs only. Besides, the metabolic stabilities of AP in the three livermicrosomes showed that the in vitro intrinsic clearance (CLint) of RLMs was much higher than that of HLMs and DLMs. CONCLUSIONS A qualitative and semi-quantitative method was developed for the identification and metabolic stabilities of AP. The general metabolic profiles between three species were clarified. Significant species differences indicated a more cautious strategy for further pharmacokinetics research of AP in animal models. Copyright (c) 2013 John Wiley & Sons, Ltd.

Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry ; Spectroscopy
WOS SubjectBiochemical Research Methods ; Chemistry, Analytical ; Spectroscopy
WOS IDWOS:000319071700013
The Source to ArticleWOS
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
2.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa, Macau, Peoples R China
Recommended Citation
GB/T 7714
Zhao, Hai-Yu,Hu, Hao,Wang, Yi-Tao. Comparative metabolism and stability of andrographolide in liver microsomes from humans, dogs and rats using ultra-performance liquid chromatography coupled with triple-quadrupole and Fourier transfor[J]. RAPID COMMUNICATIONS IN MASS SPECTROMETRY,2013,27(12):1385-1392.
APA Zhao, Hai-Yu,Hu, Hao,&Wang, Yi-Tao.(2013).Comparative metabolism and stability of andrographolide in liver microsomes from humans, dogs and rats using ultra-performance liquid chromatography coupled with triple-quadrupole and Fourier transfor.RAPID COMMUNICATIONS IN MASS SPECTROMETRY,27(12),1385-1392.
MLA Zhao, Hai-Yu,et al."Comparative metabolism and stability of andrographolide in liver microsomes from humans, dogs and rats using ultra-performance liquid chromatography coupled with triple-quadrupole and Fourier transfor".RAPID COMMUNICATIONS IN MASS SPECTROMETRY 27.12(2013):1385-1392.
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