High-performance liquid chromatography-UV diode array, inductively coupled plasma mass spectrometry (ICPMS) and orthogonal acceleration time-of-flight mass spectrometry (oa-TOFMS) applied to the simultaneous detection and identification of metabolites of 4-bromoaniline in rat urine

被引:26
作者
Abou-Shakra, FR
Sage, AB
Castro-Perez, J
Nicholson, JK
Lindon, JC
Scarfe, GB
Wilson, ID
机构
[1] Micromass UK Ltd, Manchester M23 9LZ, Lancs, England
[2] Univ London Imperial Coll Sci Technol & Med, Fac Med, London SW7 2AZ, England
[3] AstraZeneca, Dept Drug Metab & Pharmacokinet, Macclesfield SK10 4TG, Cheshire, England
关键词
HPLC-ICPMS; TOFMS; multiple hyphenation; metabolite profiling; aniline metabolism;
D O I
10.1007/BF02493345
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The use of reversed-phase gradient HPLC coupled to UV, ICPMS and oa-TOFMS for the profiling and identification of metabolites in rat urine following the administration 4-bromoaniline is described. Following chromatographic separation and UV detection the eluent was split, with the major portion of the eluent (90%) directed to an ICPMS where bromine and sulphur-containing metabolites were selectively detected using ICPMS in order to obtain a metabolite profile. The remainder of the flow (10%) was serf to an oo-TOFMS in order to obtain accurate mass data as an aid to metabolite identification. The identity of the major metabolite was confirmed as a sulphate of a ring-hydroxylated metabolite. In addition a number of peaks were identified as conjugated metabolites, including glucuronides, an N-oxanlic acid and an N-acetylcysteinyl conjugate.
引用
收藏
页码:S9 / S13
页数:5
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