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

1995; Elsevier BV; Volume: 712; Issue: 1 Linguagem: Inglês

10.1016/0021-9673(95)00288-x

1873-3778

Grace K. Poon, Florence I. Raynaud, Prakash Mistry, D.E. Odell, Lloyd R. Kèlland, Kenneth R. Harrap, C. F. J. Barnard, Barry A. Murrer,

Mass Spectrometry Techniques and Applications

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.