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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 transform ion cyclotron resonance mass spectrometry
Zhao H.-Y.; Hu H.; Wang Y.-T.
2013
Source PublicationRapid Communications in Mass Spectrometry
Volume27Issue:12Pages:1385
AbstractRATIONALE Andrographolide (AP) is a major active anti-inflammatory compound extracted from Andrographis paniculata Nees. The metabolism stability of AP 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 comparative investigation 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 liver microsomes 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 © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.
DOI10.1002/rcm.6585
URLView the original
Language英语
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorWang Y.-T.
Affiliation1.Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau
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Zhao H.-Y.,Hu H.,Wang Y.-T.. 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 transform ion cyclotron resonance mass spectrometry[J]. Rapid Communications in Mass Spectrometry,2013,27(12):1385.
APA Zhao H.-Y.,Hu H.,&Wang Y.-T..(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 transform ion cyclotron resonance mass spectrometry.Rapid Communications in Mass Spectrometry,27(12),1385.
MLA Zhao H.-Y.,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 transform ion cyclotron resonance mass spectrometry".Rapid Communications in Mass Spectrometry 27.12(2013):1385.
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