Premium
An experimental approach to enhance precursor ion fragmentation for metabolite identification studies: application of dual collision cells in an orbital trap
Author(s) -
Bushee Jennifer L.,
Argikar Upendra A.
Publication year - 2011
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.4996
Subject(s) - chemistry , fragmentation (computing) , collision induced dissociation , mass spectrometry , ion trap , quadrupole ion trap , dissociation (chemistry) , metabolite , ion , analytical chemistry (journal) , chromatography , tandem mass spectrometry , organic chemistry , biochemistry , computer science , operating system
Recent advancements in mass spectrometry including data‐dependent scanning and high‐resolution mass spectrometry have aided metabolite profiling for non‐radiolabeled xenobiotics. However, narrowing down a site of metabolism is often limited by the quality of the collision‐induced dissociation (CID)‐based precursor ion fragmentation. An alternative dissociation technique, higher energy collisional dissociation (HCD), enriches compound fragmentation and yields ‘triple‐quadrupole‐like fragmentation’. Applying HCD along with CID and data‐dependent scanning could enhance structural elucidation for small molecules. Liquid chromatography/multi‐stage mass spectrometry (LC/MS n ) experiments with CID and HCD fragmentation were carried out for commercially available compounds on a hybrid linear ion trap orbital trap mass spectrometer equipped with accurate mass measurement capability. The developed method included stepped normalized collision energy (SNCE) parameters to enhance MS fragmentation without tuning for individual compounds. All the evaluated compounds demonstrated improved fragmentation under HCD as compared with CID. The results suggest that an LC/MS n method that incorporated both SNCE HCD‐ and CID‐enabled precursor ion fragmentation afforded comprehensive structural information for the compounds under investigation. A dual collision cell approach was remarkably better than one with only CID MS n in an orbital trap. It is evident that such an acquisition method can augment the identification of unknown metabolites in drug discovery by improving fragmentation efficiency of both the parent compound and its putative metabolite(s). Copyright © 2011 John Wiley & Sons, Ltd.