A liquid chromatography electrospray ionization tandem mass spectrometric study (LC/ESI-MS/MS) of in vivo metabolites of cisplatin in rat liver and brain tissues: deuterated experiments. Issue 109 (21st October 2015)

• Record Type: Journal Article
• Authors: Bandu, Raju; Kim, Hak Jin; Mok, Hyuck Jun; Kim, Kwang Pyo
• Is Part Of: RSC advances. Volume 5:Issue 109(2015)
• Page Start: 89951
• Page End: 89958
• Publication Date: 2015-10-21
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c5ra15237b
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : In vivo rat liver and brain tissue metabolites of an anticancer drug, cisplatin, have been identified and characterized by using LC/ESI-MS/MS in combination with on-line H/D exchange experiments. Abstract : In vivo rat liver and brain tissue metabolites of an anticancer drug, cisplatin (( cis -diamminedichloroplatinum(ii )) (CP )), 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, whole liver and brain tissues were removed after intravenous administration ofCP to adult male Sprague-Dawley rats ( n = 3 per group). The liver and brain tissues were homogenized and extracted using a metabolite extraction procedure that involves liquid extraction with phosphate buffer containing ethyl acetate and protein precipitation with mixed solvents of methanol–water–chloroform followed by a solid-phase clean-up procedure on Oasis® HLB 3cc cartridges and then subjected to LC/ESI-HRMS analysis. A total of seventeen in vivo metabolites have been identified in liver tissue homogenates including mono aquaCP, monohydroxyCP, dihydroxyCP, and hydroxy aquaCP metabolites which were also observed in brain tissue homogenates. Out of the seventeen, thirteen metabolites are new, whereas the remaining four metabolites, M1–M4 were recently reported in our previous study. The structures of the metabolites were proposed using LC-MS/MS experiments and accurate mass measurements in conjunction with online deuterated experiments. These deuterated experiments were used to further support the structural characterization of drug metabolites. The identification of new metabolites provides essential information for further pharmacological and clinical studies ofCP, and may also be useful to develop effective new anticancer agents.