Identification of Major Metabolites of New Platinum(II) Complexes in Rats

새로운 백금 착체(II) 화합물의 흰쥐 혈장에서 대사체 확인

KHPC-002 $[(trans-l-diaminocyclohexane-bis-l,2(diphenylphosphinoethane)platinum)\;{\cdot}2NO_3]$ and $KHPC-006[(cis-diaminocyclohexane-bis-1,2(diphenylphosphinoethane)platinum)\;{\cdot}2NO_3]$ were synthesized as candidates for third platinum antitumor agent. Before their pharmacokinetic study, we optimized the analytical condition with HPLC and identified the major metabolites in the rat plasma. HPLC analysis by $C_{18}$ reverse-phase column showed that standard peak of both compounds appeared rapidly at around 1 minutes, whereas metabolites of KHPC-002 and KHPC-006 which were extracted from plasma after single I.V. administration in rats or incubation for 24 hr at $37^{\circ}C$ showed retention time of $10{\sim}11$ minutes. These metabolites were identified as the major compound by Matrix Associated Laser Deposition/Ionization (MALDI), which only lose the 2 molecules of $NO_3$. Based on these results, we suggest that the major metabolites of KHPC-002 and KHPC-006 were [trans-l-diamino-cyclohexane-bis-l,2(diphenylphosphinoethane)platinum] and [cis-diaminocyclohexane-bis-l.2(diphenylphosphinoethane)platinum], respectively.