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

Authors
  • Poon, G K1
  • Raynaud, F I
  • Mistry, P
  • Odell, D E
  • Kelland, L R
  • Harrap, K R
  • Barnard, C F
  • Murrer, B A
  • 1 CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK.
Type
Published Article
Journal
Journal of Chromatography A
Publisher
Elsevier
Publication Date
Sep 29, 1995
Volume
712
Issue
1
Pages
61–66
Identifiers
PMID: 8556156
Source
Medline
License
Unknown

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.

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