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)(2)Cl(SG)] and cis-{[Pt(NH3)(2)Cl](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/m(2) to patients) preceded by a GSH intravenous administration (200 mg/kg to rats as a bolus and 1.5 g/m(2) 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.

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 AND CANCER-PATIENTS / A. Bernareggi, L. Torti, R. Maffei Facino, M. Carini, G. Depta, B. Casetta, N. Farrell, S. Spadacini, R. Ceserani, S. Tognella. - In: JOURNAL OF CHROMATOGRAPHY B. BIOMEDICAL APPLICATIONS. - ISSN 0378-4347. - 669:2(1995), pp. 247-263.

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 AND CANCER-PATIENTS

R. Maffei Facino;M. Carini;
1995

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)(2)Cl(SG)] and cis-{[Pt(NH3)(2)Cl](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/m(2) to patients) preceded by a GSH intravenous administration (200 mg/kg to rats as a bolus and 1.5 g/m(2) 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.
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/185407
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