Chemical instability and methods for measurement of cisplatin adducts formed by interactions with cysteine and glutathione

Int J Clin Pharmacol Ther. 2001 Aug;39(8):344-9. doi: 10.5414/cpp39344.

Abstract

Reactions between cisplatin or its aquated species and L-cysteine (L-cys) or glutathione (GSH) were studied in vitro using liquid chromatography on-line with inductively coupled plasma mass spectrometry (LC-ICPMS) and/or electrospray ionization mass spectrometry (LC-MS) in order to obtain information on the mechanisms occurring in treated patients. Reaction between cisplatin and L-cys yielded initially 4 adducts of which only 2 were stable and detectable after 24 hours incubation; their structures corresponded to bis-platinum cysteinyl adducts. Reaction of cisplatin with GSH proceeded via the formation of at least 11 glutathione-platinum adducts (G1 - G11) which underwent parallel reactions within 24 hours of incubation, probably to form higher molecular weight species. Of the 11 adducts, only 2, G3 and G7, whose structures correspond to [Pt(NH3)2Cl]2(SG) and [Pt(NH3)2OH]2(SG) were still present in the reaction mixture after 24 hours incubation. This study shows that GSH, and to a lesser extent L-cys, incubated with cisplatin in vitro forms unstable and reactive platinum compounds and that LC-ICPMS and LC-MS are 2 complementary techniques suitable for the study of organometallic compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Chromatography, Liquid
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • Cysteine / chemistry*
  • DNA Adducts*
  • Glutathione / chemistry*
  • In Vitro Techniques
  • Spectrometry, Mass, Electrospray Ionization / methods

Substances

  • Antineoplastic Agents
  • DNA Adducts
  • Glutathione
  • Cysteine
  • Cisplatin