title: Characterization of cisplatin-glutathione adducts by liquid chromatography-mass spectrometry. Evidence for their formation in vitro but not in vivo after concomitant administration of cisplatin and glutathione to rats anc cancer patients.
abstract: After incubation of equimolar amounts of cisplatin (CDDP) and glutathione (GSH) in phosphate buffer pH 7.4 at 37 degrees C, we detected two CDDP-GSH adducts whose structures, characterized by LC-MS, corresponded to cis-[Pt(NH3)2Cl(SG)] and cis-([Pt(NH3)2Cl]2(mu-SG))+. The latter is a new CDDP-GSH adduct, which was postulated but never structurally characterized so far. Rats and patients were given a 15-min intravenous infusion of CDDP (10 mg/kg to rats and 25 mg/m2 to patients) preceded by a GSH intravenous administration (200 mg/kg to rats as a bolus and 1.5 g/m2 to patients as a 15-min infusion). After the administrations, CDDP-GSH adducts were absent in rat and human plasma ultrafiltrates. The discrepancy between in vitro and in vivo findings can be explained based on pharmacokinetic considerations.
authors.affiliation: Boehringer Mannheim Italia SpA, Research Center, Monza (MI), Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bernareggi
authors.forename: L
authors.initials: L
authors.lastname: Torti
authors.forename: R M
authors.initials: RM
authors.lastname: Facino
authors.forename: M
authors.initials: M
authors.lastname: Carini
authors.forename: G
authors.initials: G
authors.lastname: Depta
authors.forename: B
authors.initials: B
authors.lastname: Casetta
authors.forename: N
authors.initials: N
authors.lastname: Farrell
authors.forename: S
authors.initials: S
authors.lastname: Spadacini
authors.forename: R
authors.initials: R
authors.lastname: Ceserani
authors.forename: S
authors.initials: S
authors.lastname: Tognella
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D002021:Buffers; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D005978:Glutathione / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D009944:Organoplatinum Compounds / Q000097:blood*; D010710:Phosphates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013054:Spectrophotometry, Atomic; D013056:Spectrophotometry, Ultraviolet; D013736:Testicular Neoplasms / Q000097:blood* / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D002021:Buffers; D009944:Organoplatinum Compounds; D010710:Phosphates; C096772:mu-S-glutathionyl-bis(cis-diamminechloroplatinum(II)); C096771:diamminechloro(glutathionato-S)platinum(II); D005978:Glutathione; D002945:Cisplatin; C018279:sodium phosphate