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Rapid detection and characterization of minor reactive metabolites using stable‐isotope trapping in combination with tandem mass spectrometry
Author(s) -
Yan Zhengyin,
Maher Noureddine,
Torres Rhoda,
Caldwell Gary W.,
Huebert Norman
Publication year - 2005
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2195
Subject(s) - chemistry , tandem mass spectrometry , tandem , chromatography , mass spectrometry , characterization (materials science) , selected reaction monitoring , trapping , nanotechnology , ecology , materials science , composite material , biology
Stable‐isotope trapping combined with mass spectrometry (MS) neutral loss scanning has recently been developed as a high‐throughput method for the in vitro screening of major reactive metabolites. In fact, detection and identification of minor reactive metabolites are equally important since the minor metabolites, even though at low levels, may be highly reactive and also play an important role in drug‐induced adverse reactions. In this study, 2‐acetylthiophene, clozapine, troglitazone and 7‐methylindole were selected as model compounds to further validate the advantages of this method for rapid detection and structural characterization of minor glutathione (GSH) adducts derived from reactive metabolites. The utility of the current method was clearly demonstrated by successful identification of novel reactive metabolites at low levels and also minor ones either masked by non‐specific responses or co‐eluted with other conjugates. In comparison with existing methods, this method is sensitive, efficient, and suitable for rapid screening and more complete profiling of reactive metabolites. Copyright © 2005 John Wiley & Sons, Ltd.