Urinary metabolites of DX-8951, a novel camptothecin analog, in rats and humans

被引：0

作者：

Atsumi, R ^{[1
]}

Oguma, T ^{[1
]}

Yoshioka, N ^{[1
]}

Konno, T ^{[1
]}

Okazaki, O ^{[1
]}

Fujimaki, Y ^{[1
]}

机构：

[1] Daiichi Pharmaceut Co Ltd, Drug Metab & Analyt Chem Res Lab, Edogawa Ku, Tokyo 1348630, Japan

来源：

ARZNEIMITTEL-FORSCHUNG-DRUG RESEARCH | 2001年 / 51卷 / 03期

关键词：

camptothecin; derivative; CAS; 171335-80-1; cytostatics; DX-8951; human; metabolites; rat; exatecan;

D O I：

暂无

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Urinary metabolites of DX-8951 ((1S,9S)1-amino-9-ethyl-5-fluoro-1,2,3,9, 12,15-hexahydro-9 -hydroxy-4-methyl-10H,13H-benzolde] pyrano [3',4':6,7] indolizino[1,2-b] quinoline-10, 13-dione, CAS 171335-80-1, exatecan) in rats and humans were identified. Rats were dosed with the drug, and two major metabolites (UM-1 and UM-2) in the urine were isolated and purified by using ion-exchange column and HPLC. From NMR and mass spectra, they are suggested to be 4-hydroxymethyl metabolite (UM-1) and 3-hydroxy metabolite (UM-2) of the drug. Their chemical structures were confirmed by comparing their NMR spectra with those of chemically synthesized metabolites. Two major metabolites were found in human urine obtained in phase I trial. They were also confirmed to be UM-1 and UM-2 by LC/MS/MS by comparing their mass fragment patterns with those of synthetic metabolites.

引用

页码：253 / 257

页数：5

共 39 条

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