Pharmaceutical Research

, Volume 21, Issue 5, pp 891–894

Oxaliplatin Degradation in the Presence of Chloride: Identification and Cytotoxicity of the Monochloro Monooxalato Complex

Authors

    • Karolinska PharmacyKarolinska Hospital
  • Mikael Hedeland
    • Department of ChemistryNational Veterinary Institute (SVA)
  • Inger Wallin
    • Karolinska PharmacyKarolinska Hospital
  • Ulf Bondesson
    • Department of ChemistryNational Veterinary Institute (SVA)
    • Division of Analytical Pharmaceutical ChemistryUppsala University
  • Hans Ehrsson
    • Karolinska PharmacyKarolinska Hospital
    • Department of Oncology-PathologyKarolinska Institutet
Article

DOI: 10.1023/B:PHAM.0000026444.67883.83

Cite this article as:
Jerremalm, E., Hedeland, M., Wallin, I. et al. Pharm Res (2004) 21: 891. doi:10.1023/B:PHAM.0000026444.67883.83

Abstract

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.

biotransformation HT-29 Pt(dach)Cl2

Copyright information

© Plenum Publishing Corporation 2004