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.
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Jerremalm, E., Hedeland, M., Wallin, I. et al. Oxaliplatin Degradation in the Presence of Chloride: Identification and Cytotoxicity of the Monochloro Monooxalato Complex. Pharm Res 21, 891–894 (2004). https://doi.org/10.1023/B:PHAM.0000026444.67883.83
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DOI: https://doi.org/10.1023/B:PHAM.0000026444.67883.83