HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ISOLATION AND SPECTROSCOPIC CHARACTERIZATION OF 3 MAJOR METABOLITES FROM THE PLASMA OF RATS RECEIVING RAPAMYCIN (SIROLIMUS) ORALLY

被引:12
作者
WANG, CP
LIM, HK
CHAN, KW
SCATINA, J
SISENWINE, SF
机构
[1] Division of Drug Metabolism, Wveth-Ayerst Research, New Jersey, CN 8000, Princeton
来源
JOURNAL OF LIQUID CHROMATOGRAPHY | 1995年 / 18卷 / 13期
关键词
D O I
10.1080/10826079508009308
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Three major metabolites of rapamycin (M2, M3, and M5) were isolated from pooled plasma of orally dosed rats. Metabolites were extracted from the plasma with ethyl acetate/methanol prior to isolation by HPLC using a Supelcosil SPLC-18, 5 mu m, IO x 250 mm column. The mobile phase was a methanol/ammonium acetate linear gradient system. The isolated metabolites were characterized by negative ion FAB MS, ion-spray MS and ion-spray MS/MS. Metabolite M2 is oxygenated in the southern portion of rapamycin and the macrolide ring is opened. M3 is a structural isomer of rapamycin where the lactone ring is opened. M5 is O-demethylated on the C41 methoxy moiety and the macrolide ring is intact.
引用
收藏
页码:2559 / 2568
页数:10
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