Issue 109, 2015

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

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 of CP 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 aqua CP, monohydroxy CP, dihydroxy CP, and hydroxy aqua CP 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 of CP, and may also be useful to develop effective new anticancer agents.

Graphical abstract: 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

Supplementary files

Article information

Article type
Paper
Submitted
31 Jul 2015
Accepted
14 Oct 2015
First published
14 Oct 2015

RSC Adv., 2015,5, 89951-89958

Author version available

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

R. Bandu, H. J. Kim, H. J. Mok and K. P. Kim, RSC Adv., 2015, 5, 89951 DOI: 10.1039/C5RA15237B

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements