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Identification of novel metabolites of vinorelbine in rat
K Yamaguchi1, T Yasuzawa, T Sakai
1Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd, Shizuoka-ken, Japan.
Abstract:
1. Vinorelbine produced a dominant metabolite (M1) after incubation with rat liver microsomes. 2. Several major metabolites other than M1 were identified by HPLC in bile and faeces of rat after intravenous administration. 3. The structures of the major metabolites were identified as 15,16-epoxyvinorelbine (M1), 11'-hydroxyvinorelbine (M2), 19'-hydroxyvinorelbine (M3a), 15,16-epoxy-10'-hydroxyvinorelbine (M3b) and 10'-hydroxyvinorelbine (M4) by comparison of HPLC retention times and by extensive analyses of two-dimensional NMR and hybrid MS/MS spectra.
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