期刊
PHARMACEUTICAL RESEARCH
卷 21, 期 5, 页码 891-894出版社
KLUWER ACADEMIC/PLENUM PUBL
DOI: 10.1023/B:PHAM.0000026444.67883.83
关键词
biotransformation; HT-29; Pt(dach)Cl-2
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)Cl-2), 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)Cl-2 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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