期刊
JOURNAL OF MASS SPECTROMETRY
卷 39, 期 3, 页码 295-302出版社
JOHN WILEY & SONS LTD
DOI: 10.1002/jms.582
关键词
collision-induced dissociation; COX-2 inhibitor; liquid chromatography/tandem mass spectrometry; rearrangement; valdecoxib; isoxazole
Valdecoxib is a potent COX-2 inhibitor. During metabolism studies of valdecoxib by liquid chromatography/tandem mass spectrometry, we observed a novel mass spectral rearrangement involving an isoxazole ring for some of the metabolites in the negative ion mode. Accurate mass measurements were performed with quadrupole time-of-flight mass spectrometry to determine the elemental compositions of the fragments. Additionally, two types of stable-isotope labeled analogues were prepared to assist with the assignments of these fragments and possible mechanistic rearrangements resulting from collision-induced dissociation (CID). Detailed analyses of the CID mass spectra suggest that the fragmentation process involves a novel two-step rearrangement. The first step consists of an intramolecular S(N)2 reaction with a five-membered ring rearrangement to form an intermediate. The second step involves a four-membered ring intramolecular rearrangement followed by a cleavage of the N - 0 bond on the isoxazole ring to form a unique fragment ion at m/z 196. The same phenomenon was observed for a group of structurally related metabolites that also contain a 5-hydroxymethyl or 5-carboxylic acid moieties. A mechanism for the novel rearrangement involving an isoxazole ring is proposed. Copyright (C) 2004 John Wiley Sons, Ltd.
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