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 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.
Poon
G K
GK
CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK.
Mistry
P
P
Raynaud
F I
FI
Harrap
K R
KR
Murrer
B A
BA
Barnard
C F
CF
D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics*; D001711:Biotransformation; D002853:Chromatography, Liquid; D005410:Flame Ionization; D006801:Humans; D007536:Isomerism; D013058:Mass Spectrometry; D009944:Organoplatinum Compounds / Q000097:blood* / Q000493:pharmacokinetics*; D010984:Platinum / Q000097:blood; D011092:Polyethylene Glycols / Q000032:analysis; D014462:Ultrafiltration
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011092:Polyethylene Glycols; D010984:Platinum; C081294:satraplatin