Early biotransformations of oxaliplatin after its intravenous administration to cancer patients

This article deals with the fate of oxaliplatin 1 and 3 h after its i.v. ad ministration (130 mg/m(2)) to three patients. Its binding to plasma protein s and penetration into red blood cells were monitored by chromatography on- line with inductively coupled plasma mass spectrometry. Oxaliplatin biotran sformations in plasma ultrafiltrate (PUF) and in urine were studied by chro matography coupled to inductively coupled plasma mass spectrometry or to el ectrospray ionization mass spectrometry. In plasma, four platinum (Pt) comp ounds were found. The peaks at 200 and 160 kDa corresponding to gamma-globu lins contained 40% of the Pt bound; the peak at 60 kDa corresponding to alb umin contained 40% of the Pt found. The peak <2 kDa could correspond to oxa liplatin, to its degradation products, or to adducts between Pt compounds a nd low-molecular-weight species such as glutathione, L-methionine, and L-cy steine. In PUF and urine, oxaliplatin itself, its degradation products, Pt- (dach)Cl-2, [Pt(dach)(OH2)Cl](+), and species that have the same retention times as Pt(dach)(methionine) and [Pt(dach)](2)(glutathione) were found. On e hour after infusion, oxaliplatin in PUF and urine represented 12 and 50% of the total Pt, respectively. Three hours after infusion, oxaliplatin, und etectable in PUF, represented 10% of total Pt in urine. Inside red blood ce lls, two Pt compounds were found. The Pt peak at 60 kDa corresponding to he moglobin and the peak <2 kDa corresponding to low-molecular species contain ed, respectively, 60% and 40% of Pt found. This study demonstrates that in the first hours after its infusion, oxaliplatin, in addition to other Pt co mpounds, is present in plasma and urine and that Pt is bound to albumin, ga mma-globulins, and hemoglobin.