Oxaliplatin Degradation in the Presence of Chloride: Identification and Cytotoxicity of the Monochloro Monooxalato Complex
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Purpose. To study the degradation of oxaliplatin in chloride media and evaluate the cytotoxicity of oxaliplatin in normal and chloride-deficient medium.
Methods. The products of the reaction of oxaliplatin with chloride were separated on a Hypercarb S column with a mobile phase containing 40% methanol in 0.05 M ammonia and subjected to electrospray ionization mass spectrometry. The cytotoxicity of oxaliplatin in normal and chloride-deficient medium was evaluated by 30-min incubations on human colon adenocarcinoma cells (HT-29).
Results. We identified a new intermediate degradation product, the monochloro monooxalato complex ([Pt(dach)oxCl]−) and the final product, the dichloro complex (Pt(dach)Cl2), by liquid chromatography-mass spectrometry. [Pt(dach)oxCl]− was found as the negative ion, M−, at m/z 431, and the positive ion, [M+2H]+, m/z 433. Pt(dach)Cl2 was found as the negative ion, [M-H]−, m/z 377, and the positive ion, [M+NH4]+, m/z 396. The fast initial degradation of oxaliplatin can be coupled to the fast formation of [Pt(dach)oxCl]−. In the cytotoxic assay, the cell survival was not affected by the chloride levels.
Conclusions. [Pt(dach)oxCl]−, a new transformation product of oxaliplatin, has been identified. Its in vitro cytotoxic effect does not appear to exceed that of oxaliplatin.
- S. Mani, M. A. Graham, D. B. Bregman, P. Ivy, and S. G. Chaney. Oxaliplatin: a review of evolving concepts. Cancer Invest. 20:246–263 (2002).
- H. Ehrsson, I. Wallin. and J. Yachnin. Pharmacokinetics of oxaliplatin in humans. Med. Oncol. 19:261–265 (2002).
- M. A. Graham, G. F. Lockwood, D. Greenslade, S. Brienza, M. Bayssas, and E. Gamelin. Clinical pharmacokinetics of oxaliplatin: a critical review. Clin. Cancer Res. 6:1205–1218 (2000).
- P. Allain, O. Heudi, A. Cailleux, A. Le Bouil, F. Larra, M. Boisdron-Celle, and E. Gamelin. Early biotransformations of oxaliplatin after its intravenous administration to cancer patients. Drug Metab. Dispos. 28:1379–1384 (2000).
- F. R. Luo, S. D. Wyrick, and S. G. Chaney. Cytotoxicity, cellular uptake, and cellular biotransformations of oxaliplatin in human colon carcinoma cells. Oncol. Res. 10:595–603 (1998).
- P. Videhult, J. Yachnin, E. Jerremalm, R. Lewensohn, and H. Ehrsson. Synthesis and cytotoxicity of the dihydrated complex of oxaliplatin. Cancer Lett. 180:191–194 (2002).
- J. L. Butour, A. M. Mazard, and J. P. Macquet. Kinetics of the reaction of cis-platinum compounds with DNA in vitro. Biochem. Biophys. Res. Commun. 133:347–353 (1985).
- U. Frey, J. D. Ranford, and P. J. Sadler. Ring-opening reactions of the anticancer drug carboplatin: NMR characterization of cis-[Pt(NH3)2(CBDCA-O)(5′-GMP-N7)] in solution. Inorg. Chem. 32:1333–1340 (1993).
- S. S. Shord, S. A. Bernard, C. Lindley, A. Blodgett, V. Mehta, M. A. Churchel, M. Poole, S. L. Pescatore, F. R. Luo, and S. G. Chaney. Oxaliplatin biotransformation and pharmacokinetics: a pilot study to determine the possible relationship to neurotoxicity. Anticancer Res. 22:2301–2310 (2002).
- G. Siebert. The biochemical environment of the mammalian nucleus. Sub-Cell. Biochem. 1:277–292 (1972).
- Oxaliplatin Degradation in the Presence of Chloride: Identification and Cytotoxicity of the Monochloro Monooxalato Complex
Volume 21, Issue 5 , pp 891-894
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- 1. Karolinska Pharmacy, Karolinska Hospital, SE-171 76, Stockholm, Sweden
- 2. Department of Chemistry, National Veterinary Institute (SVA), SE-751 89, Uppsala, Sweden
- 3. Division of Analytical Pharmaceutical Chemistry, Uppsala University, SE-751 23, Uppsala, Sweden
- 4. Department of Oncology-Pathology, Karolinska Institutet, SE-171 76, Stockholm, Sweden