Mutagenic activity and identification of excreted platinum in human and rat urine and rat plasma after administration of cisplatin

Cisplatin and its biotransformation products were analyzed in human and rat urine and in plasma from rats. Analyses were performed using high performance liquid chromatography (HPLC). Microbial mutagenesis assays were performed on effluents from the chromatographic system. After intravenous administration to man (50 mg/m²) and intravenous and intraperitoneal administration to rats (5-10 mg/kg), platinum was excreted in the urine in a form that co-eluted mainly with cisplatin. Unbound drug in the plasma co-eluted with cisplatin. Furthermore excreted platinum exhibited mutagenic and chemical reactivity similar to that of cisplatin. We conclude that the principal form of free platinum circulating in blood and excreted in urine is cisplatin.