Abstract

Symposium Sessions

Day 2, June 11（Tue.）　10:23-10:45　Room C (Conference Room 201)

Xenobiotics such as pharmaceuticals, pesticides, and environmental pollutants are metabolized to many chemical substances by various enzymes in a living organism. In general, xenobiotic metabolites have a lower pharmacological activity and toxicity than does the unmodified xenobiotic, but some can show increased pharmacological and/or toxicological activity, inducing carcinogenesis, malformations, and various organ toxicity. Therefore, comprehensive and accurate understanding of xenobiotic metabolism is needed to safely and effectively develop xenobiotics. More importantly, understanding how the endogenous metabolism is affected by the xenobiotic and its metabolites is essential to elucidate the mechanism of action. In this session, I will talk about an advanced method to detect and identify comprehensive xenobiotic metabolites using liquid chromatography coupled with benchtop quadrupole Orbitrap high-resolution tandem mass spectrometry (LC/HRMS/MS), data mining techniques, and in silico metabolism prediction. Furthermore, I will provide a new hepatotoxicity evaluation method based on multi-omics analysis (xenobiotic metabolism analysis, metabolomics, and proteomics) of 5×10⁴ primary human hepatocytes (PHH) cultured in a 96-well plate, which is equivalent to 1/100th of the number of cells used in conventional methods.

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