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새로운 백금 착체(2) 화합물의 흰쥐 혈장에서 대사체 확인
Identification of Major Metabolites of New Platinum(2) Complexes in Rats
김종환(Jong Whan Kim), 조요나(Yo Na Jo), 노영수(Young Soo Rho), 서성훈(Seong Hoon Seo), 정지창(Jee Chang Jung), 장성구(Sung Goo Chang), 이규홍(Kyoe Heung Lee), 이주한(Joo Han Lee), 이경태(Kyung Tae Lee)
UCI I410-ECN-0102-2008-510-001525332

KHPC-002[(trans-l-diaminocyclohexane-bis-1,2(diphenylphosphinoethane)platinum)·2NO₃] and KHPC-006[(cis-diaminocyclohexane-bis-1,2(diphenylphosphinoethane)platinum)·2NO₃] 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℃ showed retention time of 10∼11 minutes. These metabolites were identified as the major compound by Matrix Associated Laser Deposition/Ionization (MALDI), which only lose the 2 molecules of NO₃. Based on these results, we suggest that the major metabolites of KHPC-002 and KHPC-006 were [trans-l-diamino-cyclohexane-bis-1, 2(diphenylphosphinoethane)platinum] and [cis-diaminocyclohexane-bis-1,2(diphenylphosphinoethane)platinum], respectively.

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