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.
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 humancolon 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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