Determination of metabolites of a novel platinum anticancer drug JM216 in human plasma ultrafiltrates

The present study describes the application of on-line liquid chromatography-electrospray ionisation in conjunction with a high resolution magnetic sector mass spectrometer to identify metabolites of a platinum(IV) anticancer drug JM216 bis(acetato)amminedichloro(cyclohexylamine)platinum(IV)] in hum...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 1995-11, Vol.13 (12), p.1493-1498
Main Authors: Poon, G.K., Mistry, P., Raynaud, F.I., Harrap, K.R., Murrer, B.A., Barnard, C.F.J.
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - blood
Antineoplastic Agents - pharmacokinetics
Biological and medical sciences
Biotransformation
Chemotherapy
Chromatography, Liquid
Electrospray ionisation/mass spectrometry
Flame Ionization
human plasma ultrafiltrate
Humans
Isomerism
Mass Spectrometry
Medical sciences
Metabolites
Organoplatinum Compounds - blood
Organoplatinum Compounds - pharmacokinetics
Pharmacology. Drug treatments
Platinum - blood
Platinum anticancer drug
Polyethylene Glycols - analysis
Ultrafiltration
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Summary:The present study describes the application of on-line liquid chromatography-electrospray ionisation in conjunction with a high resolution magnetic sector mass spectrometer to identify metabolites of a platinum(IV) anticancer drug JM216 bis(acetato)amminedichloro(cyclohexylamine)platinum(IV)] in human plasma. Four metabolites were identified following incubation of JM216 in human plasma: JM118 [amminedichlorocyclohexylamineplatinum(II)], a platinum(II) complex; JM383 [bis(acetato)amminedihydroxo(cyclohexylamine)platinum(IV)]; JM518 [bis(acetato)amminechloro(cyclohexylamine)hydroxoplatinum(IV)] and its isomer JM559. The platinum complexes mass spectra were dominated by the natriated [M + Na] + ion. Elemental compositions of these natriated ions were confirmed by accurate mass measurement on a magnetic sector mass spectrometer in the course of LC/MS analysis. This study demonstrates the capability of direct LC-ESI/MS with accurate mass measurement for analysis of platinum complexes in biological samples. Our results suggest that LC-ESI/MS is a powerful technique for structure elucidation of novel metabolites, and could make valuable contributions to drug metabolism research.
ISSN:0731-7085
1873-264X
DOI:10.1016/0731-7085(95)01571-X