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Updated: May 10, 2026
Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
Published on: March 28, 2017
Comparative metabolism study of β-lapachone in mouse, rat, dog, monkey, and human liver microsomes using liquid
Sangkyu Lee1, In Sook Kim, Tae Hwan Kwak
1College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
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.
