High-performance liquid chromatographic separation of the biotransformation products of oxaliplatin |
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| Authors: | Feng R Luo Ten-Yang Yen Steven D Wyrick Stephen G Chaney |
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| Institution: | a Department of Biochemistry and Biophysics, Curriculum in Toxicology, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;b Department of Environmental Science and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;c Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA |
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| Abstract: | A novel single reversed-phase HPLC system was developed for separating oxaliplatin 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 biotransformation products Pt(dach)Cl2, Pt(dach)(GSH) and Pt(dach)(GSH)2 could also be resolved from other Pt-dach complexes. Among these biotransformation products, the identification of Pt(dach)(Met) was further confirmed by LC–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 isotope labeling. This HPLC technique should prove useful for separating and identifying the biotransformation products of Pt-dach drugs such as oxaliplatin, ormaplatin and Pt(dach)(mal) in biological fluids. This will allow a more 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. |
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| Keywords: | Oxaliplatin |
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