High-performance liquid chromatographic separation of the biotransformation products of oxaliplatin

A novel single reversed-phase HPLC system was developed for separating oxal iplatin and its biotransformation products formed in rat plasma. The major stable biotransformation products of oxaliplatin formed in rat plasma were identified as Pt(dach)(Cys)(2), Pt(dach)(Met) and free dach. The minor biot ransformation products Pt(dach)Cl-2, Pt(dach)(GSH) and Pt(dach)(GSH), could also be resolved from other Pt-dach complexes. Among these biotransformati on products, the identification of Pt(dach)(Met) was further confirmed by L C-ESI-MS, and the identification of Pt(dach)(Cys)(2) Pt(dach)(GSH), Pt(dach )(GSH)(2) and free dach was confirmed by atomic absorption and double isoto pe labeling. This HPLC technique should prove useful for separating and ide ntifying the biotransformation products of Pt-dach drugs such as oxaliplati n, ormaplatin and Pt(dach)(mal) in biological fluids. This will allow a mor e complete characterization of the pharmacokinetics and biotransformations of these Pt-dach drugs, which should in turn lead to a better understanding of the mechanisms leading to their toxicity and efficacy. (C) 1999 Elsevie r Science BN, All rights reserved.