Metabolic studies of an orally active platinum anticancer drug by liquid chromatography-electrospray ionization mass spectrometry

J Chromatogr A. 1995 Sep 29;712(1):61-6. doi: 10.1016/0021-9673(95)00288-x.

Abstract

Bis(acetato)amminedichloro(cyclohexylamine) platinum(IV) (JM216) is a new orally administered platinum complex with antitumor properties, and is currently undergoing phase II clinical trials. When JM216 was incubated with human plasma ultrafiltrate, 93% of the platinum species were protein-bound and 7% were unbound. The unbound platinum complexes in the ultrafiltrates of human plasma were analysed using a liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method. Apart from the parent drug, four metabolites were identified and characterised. These include JM118 [amminedichloro(cyclohexylamine) platinum(II)], JM383 [bis(acetato)ammine(cyclohexylamine)dihydroxo platinum(IV)] and the two isomers JM559 and JM518 [bis(acetato)amminechloro(cyclohexylamine) hydroxo platinum(IV)]. Their elemental compositions were determined by accurate mass measurement during the LC analysis, to confirm their identities. Quantitation of these metabolites by off-line LC atomic absorption spectroscopy demonstrated that JM118 is the major metabolite in plasma from patients receiving JM216 treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / blood*
  • Antineoplastic Agents / therapeutic use
  • Chromatography, High Pressure Liquid* / methods
  • Female
  • Humans
  • Ions
  • Mass Spectrometry* / methods
  • Organoplatinum Compounds / blood*
  • Organoplatinum Compounds / therapeutic use
  • Ovarian Neoplasms / drug therapy
  • Tumor Cells, Cultured
  • Ultrafiltration

Substances

  • Antineoplastic Agents
  • Ions
  • Organoplatinum Compounds
  • amminedichloro(cyclohexylamine)platinum(II)
  • satraplatin