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 et al., 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, Journal of chromatography B. Biomedical applications, 669(2), 1995, pp. 247-263
Citations number
27
Categorie Soggetti
Chemistry Analytical","Biochemical Research Methods
Journal title
Journal of chromatography B. Biomedical applications
After incubation of equimolar amounts of cisplatin (CDDP) and glutathi
one (GSH) in phosphate buffer pH 7.4 at 37 degrees C, we detected two
CDDP-GSH adducts whose structures, characterized by LC-MS, corresponde
d 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 struc
turally characterized so far. Rats and patients were given a 15-min in
travenous infusion of CDDP (10 mg/kg to rats and 25 mg/m(2) to patient
s) 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 ad
ministrations, CDDP-GSH adducts were absent in rat and human plasma ul
trafiltrates. The discrepancy between in vitro and in vivo findings ca
n be explained based on pharmacokinetic considerations.