Allain P, Heudi O, Cailleux A, Le Bouil A, Larra F, Boisdron-Celle M, Gamelin E
Laboratoire de Pharmacologie et Toxicologie, Centre Hospitalier Universitaire, Angers, France.
Drug Metab Dispos. 2000 Nov;28(11):1379-84.
This article deals with the fate of oxaliplatin 1 and 3 h after its i.v. administration (130 mg/m(2)) to three patients. Its binding to plasma proteins and penetration into red blood cells were monitored by chromatography on-line with inductively coupled plasma mass spectrometry. Oxaliplatin biotransformations in plasma ultrafiltrate (PUF) and in urine were studied by chromatography coupled to inductively coupled plasma mass spectrometry or to electrospray ionization mass spectrometry. In plasma, four platinum (Pt) compounds were found. The peaks at 200 and 160 kDa corresponding to gamma-globulins contained 40% of the Pt bound; the peak at 60 kDa corresponding to albumin contained 40% of the Pt found. The peak <2 kDa could correspond to oxaliplatin, to its degradation products, or to adducts between Pt compounds and low-molecular-weight species such as glutathione, L-methionine, and L-cysteine. In PUF and urine, oxaliplatin itself, its degradation products, Pt(dach)Cl(2), Pt(dach)(OH(2))Cl, and species that have the same retention times as Pt(dach)(methionine) and Pt(dach)(glutathione) were found. One hour after infusion, oxaliplatin in PUF and urine represented 12 and 50% of the total Pt, respectively. Three hours after infusion, oxaliplatin, undetectable in PUF, represented 10% of total Pt in urine. Inside red blood cells, two Pt compounds were found. The Pt peak at 60 kDa corresponding to hemoglobin and the peak <2 kDa corresponding to low-molecular species contained, respectively, 60% and 40% of Pt found. This study demonstrates that in the first hours after its infusion, oxaliplatin, in addition to other Pt compounds, is present in plasma and urine and that Pt is bound to albumin, gamma-globulins, and hemoglobin.
本文研究了3名患者静脉注射奥沙利铂（130mg/m²）后1小时和3小时的情况。通过在线色谱-电感耦合等离子体质谱法监测其与血浆蛋白的结合及向红细胞内的渗透。采用色谱-电感耦合等离子体质谱法或电喷雾电离质谱法研究血浆超滤液（PUF）和尿液中奥沙利铂的生物转化。在血浆中，发现了4种铂（Pt）化合物。对应于γ-球蛋白的200和160kDa处的峰含有40%的结合铂；对应于白蛋白的60kDa处的峰含有所发现铂的40%。小于2kDa的峰可能对应奥沙利铂、其降解产物或铂化合物与低分子量物质（如谷胱甘肽、L-甲硫氨酸和L-半胱氨酸）之间的加合物。在PUF和尿液中，发现了奥沙利铂本身、其降解产物、Pt(dach)Cl₂、[Pt(dach)(OH₂)Cl]⁺以及保留时间与Pt(dach)(甲硫氨酸)和[Pt(dach)]₂(谷胱甘肽)相同的物质。输注1小时后，PUF和尿液中的奥沙利铂分别占总铂的12%和50%。输注3小时后，PUF中未检测到奥沙利铂，其在尿液中占总铂的10%。在红细胞内，发现了2种铂化合物。对应于血红蛋白的60kDa处的铂峰和对应于低分子量物质的小于2kDa的峰分别含有所发现铂的60%和40%。该研究表明，在输注后的最初几个小时内，除其他铂化合物外，奥沙利铂存在于血浆和尿液中，且铂与白蛋白、γ-球蛋白和血红蛋白结合。
