Identification of a Tryptanthrin Metabolite in Rat Liver Microsomes by Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry

Tryptanthrin originally isolated from Isatis tinctoria L. has been characterized to have anti-inflammatory activities through the dual inhibition of cyclooxygenase-2 and 5-lipoxygenase mediated prostaglandin and leukotriene syntheses. To characterize phase I metabolite(s), tryptanthrin was incubated...

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Bibliographic Details
Published in:Biological & Pharmaceutical Bulletin 2007/10/01, Vol.30(10), pp.1991-1995
Main Authors: Lee, Sang Kyu, Kim, Ghee Hwan, Kim, Dong Hyeon, Kim, Dong Hyun, Jahng, Yurngdong, Jeong, Tae Cheon
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - analysis
Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics
Biotransformation
Chromatography, High Pressure Liquid
Cytochrome P-450 Enzyme Inhibitors
cytochrome P450 (CYP)
Enzyme Inhibitors - pharmacology
In Vitro Techniques
Isatis - chemistry
LC-ESI/MS
Male
metabolite
Microsomes, Liver - chemistry
Proadifen - pharmacology
Quinazolines - analysis
Quinazolines - pharmacokinetics
rat liver microsome
Rats
Rats, Sprague-Dawley
Spectrometry, Mass, Electrospray Ionization
Spectrophotometry, Ultraviolet
Tandem Mass Spectrometry
tryptanthrin
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Summary:Tryptanthrin originally isolated from Isatis tinctoria L. has been characterized to have anti-inflammatory activities through the dual inhibition of cyclooxygenase-2 and 5-lipoxygenase mediated prostaglandin and leukotriene syntheses. To characterize phase I metabolite(s), tryptanthrin was incubated with rat liver microsomes in the presence of NADPH-generating system. One metabolite was identified by liquid chromatography/electrospray ionization-tandem mass spectrometry. M1 could be identified as a metabolite mono-hydroxylated on the aromatic ring of indole moiety from the MS2 spectra of protonated tryptanthrin and M1. The structure of metabolite was confirmed as 8-hydroxytryptanthrin with a chemically synthesized authentic standard. The formation of M1 was NADPH-dependent and was inhibited by SKF-525A, a general CYP-inhibitor, indicating the cytochrome P450 (CYP)-mediated reaction. In addition, it was proposed that M1 might be formed by CYP 1A in rat liver microsomes from the experiments with enriched rat liver microsomes.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.30.1991