Identification of cis-dichloro-bis-isopropylamine platinum(II) as a major metabolite of iproplatin in humans.
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.
Pendyala
L
L
Department of Clinical Pharmacology and Therapeutics, Roswell Park Memorial Institute, Buffalo, New York 14263.
Cowens
J W
JW
Chheda
G B
GB
Dutta
S P
SP
Creaven
P J
PJ
D000970:Antineoplastic Agents / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D006801:Humans; D009944:Organoplatinum Compounds / Q000378:metabolism*; D010084:Oxidation-Reduction
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C024235:bis(isopropylamine)dichloroplatinum; C023359:iproplatin; D004247:DNA