Metabolism of docetaxel in mice

被引：15

作者：

Bardelmeijer, HA ^{[1
]}

Roelofs, ABGH ^{[1
]}

Hillebrand, MJX ^{[1
]}

Beijnen, JH ^{[1
]}

Schellens, JHM ^{[1
]}

van Tellingen, O ^{[1
]}

机构：

[1] Netherlands Canc Inst, Antoni Van Leeuwenhoek Hosp, Dept Clin Chem, NL-1066 CX Amsterdam, Netherlands

来源：

CANCER CHEMOTHERAPY AND PHARMACOLOGY | 2005年 / 56卷 / 03期

关键词：

docetaxel; metabolites; mice; feces; bile;

D O I：

10.1007/s00280-004-0945-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Previous studies have shown by quantification of the parent drug and the known metabolites M-1, M-2, M-3 and M-4 that the mass balance of docetaxel in mice and humans is not complete. We therefore used reversed-phase high-performance liquid chromatography (HPLC) with photodiode array (PDA) detection and tandem mass spectrometry to trace and identify putative metabolites in the feces and bile of mice injected intravenously with docetaxel. HPLC-PDA revealed two metabolic products in the feces and more than ten potential new metabolites in the bile. Mass spectrometry was performed on docetaxel reference compound, on the known metabolites M-1, M-2, M-3 and M-4, and on HPLC eluate fractions containing metabolic products, six fractions originating from the bile and two from the feces. The mass spectra of the most abundant unknown metabolite in the bile and the feces were identical, and indicated that this structure contained a carboxyl moiety at the tert-butyl group. Under the conditions of storage this product degraded to metabolite M-4. All other unknown metabolites found in the bile samples were oxidized products, with the oxidations in both the C-13 side chain and the baccatin structure, the latter being a new finding.

引用

页码：299 / 306

页数：8

共 15 条

[1]

Bardelmeijer HA, 2002, CANCER RES, V62, P6158

[2] DOCETAXEL (TAXOTERE(R)) - A REVIEW OF PRECLINICAL AND CLINICAL-EXPERIENCE .1. PRECLINICAL EXPERIENCE [J].