Investigational study of tamoxifen phase I metabolites using chromatographic and spectroscopic analytical techniques

被引：20

作者：

Teunissen, S. F. ^{[1
]}

Rosing, H. ^{[1
]}

Seoane, M. Dominguez ^{[2
]}

Brunsveld, L. ^{[2
,3
]}

Schellens, J. H. M. ^{[4
,6
]}

Schinkel, A. H. ^{[5
]}

Beijnen, J. H. ^{[1
,6
]}

机构：

[1] Slotervaart Hosp, Netherlands Canc Inst, Dept Pharm & Pharmacol, NL-1066 EC Amsterdam, Netherlands

[2] Max Planck Gesell, Chem Genom Ctr, Dortmund, Germany

[3] Eindhoven Univ Technol, Dept Biomed Engn, Biol Chem Lab, NL-5600 MB Eindhoven, Netherlands

[4] Netherlands Canc Inst, Dept Clin Pharmacol, NL-1066 CX Amsterdam, Netherlands

[5] Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands

[6] Univ Utrecht, Fac Sci, Dept Pharmaceut Sci, Utrecht, Netherlands

来源：

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS | 2011年 / 55卷 / 03期

关键词：

Fragmentation; Identification; Liquid chromatography; Metabolites; Mass spectrometry; Tamoxifen; UV absorption; PERFORMANCE LIQUID-CHROMATOGRAPHY; HUMAN CYTOCHROME-P450 ENZYMES; BREAST-CANCER; LIVER-MICROSOMES; IDENTIFICATION; DROLOXIFENE; RAT; PLASMA; SERUM;

D O I：

10.1016/j.jpba.2011.02.009

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

A comprehensive overview is presented of currently known phase I metabolites of tamoxifen consisting of their systematic name and molecular structure. Reference standards are utilized to elucidate the MSn fragmentation patterns of these metabolites using a linear ion trap mass spectrometer. UV-absorption spectra are recorded and absorption maxima are defined. Serum extracts from ten breast cancer patients receiving 40 mg tamoxifen once daily were qualitatively analyzed for tamoxifen phase I metabolites using a liquid chromatography-tandem mass spectrometry set-up. In total, 19 metabolites have been identified in these serum samples. Additionally a synthetic method for the preparation of the putative metabolite 3',4'-dihydroxytamoxifen is described. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：518 / 526

页数：9

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