title: Identification of cis-dichloro-bis-isopropylamine platinum(II) as a major metabolite of iproplatin in humans.
abstract: Iproplatin is a quadrivalent second-generation platinum complex undergoing clinical evaluation. In plasma and urine of patients receiving this drug, iproplatin- and platinum-containing metabolites of iproplatin were separated by reverse-phase gradient high performance liquid chromatography. One of the metabolites was identified by cochromatography and electron impact mass spectrometry as cis-dichloro-bisisopropylamineplatinum(II), a metabolite formed by reduction of iproplatin. Incubation of iproplatin with ascorbic acid and cysteine, in vitro, indicates that iproplatin can be easily reduced to cis-dichloro-bis-isopropylamineplatinum(II) by reducing agents. It is hypothesized that the reduction of the quadrivalent complex iproplatin to cis-dichloro-bisisopropylamineplatinum(II) occurs intracellularly.
authors: Department of Clinical Pharmacology and Therapeutics, Roswell Park Memorial Institute, Buffalo, New York 14263.
authors: L
authors: L
authors: Pendyala
authors: J W
authors: JW
authors: Cowens
authors: G B
authors: GB
authors: Chheda
authors: S P
authors: SP
authors: Dutta
authors: P J
authors: PJ
authors: Creaven
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D006801:Humans; D009944:Organoplatinum Compounds / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C024235:bis(isopropylamine)dichloroplatinum; C023359:iproplatin; D004247:DNA