演題概要

2C-S-1023

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高分解能質量分析を基盤とした外因性化学物質のin vitro安全性評価法の開発

(¹九大生医研・ ²新大院医歯)
^o高橋政友¹・ 池田和輝¹・ 秦康祐¹・ 松本雅樹²・ 馬場健史¹・ 和泉自泰¹

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.