home > articles > cancer > 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.
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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.
Bernareggi A, Torti L, Facino RM, Carini M, Depta G, Casetta B, Farrell N,
Spadacini S, Ceserani R, Tognella S.
J Chromatogr B Biomed Appl. 1995 Jul 21;669(2):247-63.
SUMMARY
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.
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