Volume 22, Issue 1 p. 52-58
Research Article

Characterization of in vitro metabolites of deoxypodophyllotoxin in human and rat liver microsomes using liquid chromatography/tandem mass spectrometry

Sang Kyu Lee

Sang Kyu Lee

Doping Control Center, Korea Institute of Science and Technology, P.O. Box 131, Chungryang, Seoul 136-791, Korea

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In Hye Jun

In Hye Jun

College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea

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Hye Hyun Yoo

Hye Hyun Yoo

Doping Control Center, Korea Institute of Science and Technology, P.O. Box 131, Chungryang, Seoul 136-791, Korea

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Ju Hyun Kim

Ju Hyun Kim

College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea

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Young Min Seo

Young Min Seo

College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea

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Mi Jeong Kang

Mi Jeong Kang

College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea

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Seung Ho Lee

Seung Ho Lee

College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea

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Tae Cheon Jeong

Corresponding Author

Tae Cheon Jeong

College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea

Tae Cheon Jeong, College of Pharmacy, Yeungnam University, Gyeongsan 712-749, South Korea.

Dong Hyun Kim, Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Chungryang, Seoul 136-791, South Korea.

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Dong Hyun Kim

Corresponding Author

Dong Hyun Kim

Doping Control Center, Korea Institute of Science and Technology, P.O. Box 131, Chungryang, Seoul 136-791, Korea

Tae Cheon Jeong, College of Pharmacy, Yeungnam University, Gyeongsan 712-749, South Korea.

Dong Hyun Kim, Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Chungryang, Seoul 136-791, South Korea.

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First published: 29 November 2007
Citations: 11

Abstract

The in vitro metabolism of deoxypodophyllotoxin (DPT), a medicinal herbal product isolated from Anthriscus sylvestris (Apiaceae), was investigated in rats and human microsomes and human recombinant cDNA-expressed CYPs. The incubation of DPT with pooled human microsomes in the presence of NADPH generated five metabolites while its incubation with dexamethasone (Dex)-induced rat liver resulted in seven metabolites (M1–M7) with major metabolic reactions including mono-hydroxylation, O-demethylation and demethylenation. Reasonable structures of the seven metabolites of DPT could be proposed, based on the electrospray tandem mass spectra. Chemical inhibition by ketoconazole and metabolism studies with human recombinant cDNA-expressed CYPs indicated that CYP 3A4 and 2C19 are the major CYP isozymes in the metabolism of DPT in human liver microsomes. Copyright © 2007 John Wiley & Sons, Ltd.