Oxaliplatin degradation in the presence of chloride: identification and cytotoxicity of the monochloro monooxalato complex.
OBJECTIVE
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.
Jerremalm
Elin
E
Karolinska Pharmacy, Karolinska Hospital, SE-171 76 Stockholm, Sweden. Elin.Jerremalm@telia.com
Hedeland
Mikael
M
Wallin
Inger
I
Bondesson
Ulf
U
Ehrsson
Hans
H
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry; D002853:Chromatography, Liquid; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D006801:Humans; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology*; D000077150:Oxaliplatin; D021241:Spectrometry, Mass, Electrospray Ionization; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D002712:Chlorides; D003470:Culture Media; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin