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This study evaluated the impact of calcium and magnesium on the  in vitro  degradation and  in vivo  clearance of oxaliplatin. Intact oxaliplatin and Pt(DACH)Cl 2  were measured in incubation solutions by HPLC-UV. A clinical study determined changes in plasma concentrations of calcium and magnesium in cancer patients and their impact on oxaliplatin clearance. Kinetic analyses modelled oxaliplatin degradation reactions  in vitro  and contributions to oxaliplatin clearance  in vivo . Calcium and magnesium accelerated oxaliplatin degradation to Pt(DACH)Cl 2  in chloride-containing solutions  in vitro . Kinetic models based on calcium and magnesium binding to a monochloro-monooxalato ring-opened anionic oxaliplatin intermediate fitted the  in vitro  degradation time-course data. In cancer patients, calcium and magnesium plasma concentrations varied and were increased by giving calcium gluconate and magnesium sulfate infusions, but did not alter or correlate with oxaliplatin clearance. The intrinsic  in vitro  clearance of oxaliplatin attributed to chloride-, calcium- and magnesium-mediated degradation predicted contributions of <2.5% to the total  in vivo  clearance of oxaliplatin. In conclusion, calcium and magnesium accelerate the  in vitro  degradation of oxaliplatin by binding to a monochloro-monooxalato ring-opened anionic intermediate. Kinetic analysis of  in vitro  oxaliplatin stability data can be used for  in vitro  prediction of potential effects on oxaliplatin clearance  in vivo .

Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation