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  • 09월 08일 17시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제116회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Applications of LC-MS/MS and online H/D exchange experiments in metabolite identification and tissue distribution studies of an anticancer drug, cisplatin in rat kidney, liver and brain cancer tissues

2015년 8월 27일 16시 22분 18초
ANAL.P-326 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
10월 16일 (금요일) 13:00~14:30
저자 및
RAJU BANDU, 김광표1,*
경희대학교 응용화학과, India
1경희대학교 응용화학과, Korea
In vivo rat kidney, liver and brain tissue metabolites of an anticancer drug, cisplatin (CP), used for the treatment of mainly testicular and ovarian cancers, have been identified and characterized by using liquid chromatography positive ion electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) in combination with on line hydrogen/deuterium exchange (HDX) experiments. To identify in vivo metabolites, kidney, liver and brain tissues were collected after intravenous administration of CP to rats (n=3 per group). A total of thirty one, seventeen and four in vivo metabolites have been identified in kidney, liver and brain tissue homogenates, respectively. The structures of metabolites were elucidated based on fragmentation pattern using LC-MS/MS and accurate mass measurements combined with HDX experiments. These HDX experiments were used to further support the structural characterization of drug metabolites. The results showed that CP undergoes a series of ligand exchange biotransformation reactions with water and other nucleophiles like thio groups of methionine, cysteine, acetylcysteine, glutathione, thioether and thiol. Further, the developed LC/ESI-MS/MS method was successfully applied to investigate the distribution of CP in kidney, liver and brain tissues after intravenous administration of CP to rats. The results showed that the higher amount of CP was distributed in kidney followed by liver and brain which indicated that CP mainly accumulated in kidney tissues and renal excretion might be a primary and main elimination route. The identification of metabolites and distribution of CP in rats provide an essential information for further pharmacological and clinical studies of CP, and may also be useful to develop various effective new anticancer agents.