An experimental approach to enhance precursor ion fragmentation for metabolite identification studies: application of dual collision cells in an orbital trap
Article first published online: 18 APR 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Rapid Communications in Mass Spectrometry
Volume 25, Issue 10, pages 1356–1362, 30 May 2011
How to Cite
Bushee, J. L. and Argikar, U. A. (2011), An experimental approach to enhance precursor ion fragmentation for metabolite identification studies: application of dual collision cells in an orbital trap. Rapid Commun. Mass Spectrom., 25: 1356–1362. doi: 10.1002/rcm.4996
- Issue published online: 18 APR 2011
- Article first published online: 18 APR 2011
- Manuscript Accepted: 26 FEB 2011
- Manuscript Revised: 4 FEB 2011
- Manuscript Received: 14 DEC 2010
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/MSn) 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/MSn 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 MSn 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.