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Application of polarity switching in the identification of the metabolites of RO9237
Author(s) -
Fitch William L.,
He Limin,
Tu YaPing,
Alexandrova Ludmila
Publication year - 2007
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.3009
Subject(s) - chemistry , polarity (international relations) , identification (biology) , chromatography , biochemistry , botany , cell , biology
Polarity switching mass spectrometry is an efficient way to collect structural data on drug metabolites. The value of this approach is illustrated with the in vitro metabolism of RO9237. Metabolites are identified by positive and negative electrospray ionization (ESI) full scan mass spectrometry, MS/MS and MS 3 using unlabelled and 14 C‐radiolabelled versions of the drug. Comparison of the relative detectability of these metabolites by +ESI and −ESI shows that neither ESI mode is universal. It is advantageous to screen for metabolites using both positive and negative ionization modes. This is especially true for phase II metabolism which tends to make molecules more polar and often more acidic. Identification of phase II metabolites also benefits greatly from MS 3 experiments because the conjugating groups typically are cleaved in MS/MS and information on the core structure is only obtained in MS 3 . A special case of phase II metabolism is the generation of glutathione (GSH) conjugates from reactive metabolites. The detection of GSH conjugates also benefits from generating both positive and negative ESI mass spectral data. Copyright © 2007 John Wiley & Sons, Ltd.