Table of Contents
Metal-Based Drugs
Volume 4 (1997), Issue 2, Pages 97-109
http://dx.doi.org/10.1155/MBD.1997.97

Determination of Biotransformation Products of Platinum Drugs in Rat and Human Urine

1Barrett Center for Cancer Prevention, Treatment and Research, Cincinnati 45267, OH, USA
2College of Pharmacy, University of Cincinnati, Cincinnati 45267, OH, USA
3Department of Chemistry, Florida State University, Tallahassee 323006-30006, FL, USA
4Biomedical Chemistry Research Center, Department of Chemistry, University of Cincinnati, Cincinnati 45221-0172, OH, USA

Received 12 March 1997; Accepted 7 April 1997

Copyright © 1997 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cisplatin is an extremely effective cancer chemotherapeutic agent, but its use is often accompanied by toxicity. Second generation drugs such as carboplatin are becoming more widely used because of reduced toxicity. Since biotransformation products have been implicated in the toxic responses, we have begun to investigate the reactions of cisplatin and carboplatin with potential biological ligands. Reaction products were characterized using HPLC with inductively coupled plasma - mass spectrometry (HPLC-ICP-MS), H1 and C13 NMR and fast atom bombardment - mass spectrometry (FAB-MS). Three Pt-creatinine complexes, cis-[Pt(NH3)2Cl(Creat)]+, cis-[Pt(NH3)2(H2O)(Creat)]2+ and cis-[Pt(NH3)2(Creat)2]2+, were synthesized and the platinum was shown to coordinate to the ring nitrogen, N(3). Human urine samples from patients on cisplatin chemotherapy were shown to contain cisplatin, its hydrolysis product and biotransformation products containing Pt-creatinine, Pt-urea and Pt-uric acid complexes. Urine from carboplatin patients shows fewer biotransformation products. Studies with control and diabetic (protected against cisplatin toxicity) rats showed systematic differences in the biotransformation products formed on administration of cisplatin.