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Comparative metabolism study of β-lapachone in mouse, rat, dog, monkey, and human liver microsomes using liquid chromatography-tandem mass spectrometry
- Source :
- Journal of pharmaceutical and biomedical analysis. 83
- Publication Year :
- 2013
-
Abstract
- β-Lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione) is a natural compound extracted from the bark of the lapacho tree (Tabebuia avellanedae) and is undergoing phase II clinical trials as an antitumor drug candidate. The present study characterized in vitro metabolites of β-lapachone in mouse, rat, dog, monkey and human liver microsomes. β-Lapachone (10 μM) was incubated with mouse, rat, dog, monkey, and human liver microsomes in the presence of NADPH. The reaction mixtures were analyzed by LC/MS and the metabolites were identified based on their elemental composition and product ion spectra. A total of 6 metabolites (M1-M6) were detected in liver microsomes with a slight difference between species. M1 and M6 were identified as a decarbonated metabolite and a carboxylated metabolite, respectively; M2, M3, and M4 were identified as monohydroxylated metabolites; and M5 was identified as an O-methylated metabolite. M5, an O-methylated metabolite was found in rat and human liver microsomes, which is thought to be formed from a catechol intermediate by MB-COMT-mediated methylation and reported here for the first time.
- Subjects :
- Metabolite
Clinical Biochemistry
Pharmaceutical Science
Tandem mass spectrometry
Analytical Chemistry
chemistry.chemical_compound
Mice
Dogs
Liquid chromatography–mass spectrometry
Tandem Mass Spectrometry
Drug Discovery
Animals
Humans
Spectroscopy
Catechol
Chromatography
biology
Chemistry
Haplorhini
Methylation
biology.organism_classification
In vitro
Rats
Biochemistry
Microsome
Microsomes, Liver
NADP
Chromatography, Liquid
Naphthoquinones
Subjects
Details
- ISSN :
- 1873264X
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Journal of pharmaceutical and biomedical analysis
- Accession number :
- edsair.doi.dedup.....e7709505c7eff647226eeff4915193bd