Gérard Hopfgartner1, David Ruskic1, Patrick Mueller1, Ron Bonner2
1Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, 24 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland
LC-MS/MS-based global metabolomics or forensic investigations with electrospray ionization rely on exact mass determinations, collision induced spectra and statistical analysis for compounds detection and structural identification. The use of large MS/MS libraries, in silico fragmentation and LC retention prediction tools plays more and more an important role to achieve that goal. Beside large ionization response range, metabolites do often not generate fragment rich CID spectra for protonated and deprotonated precursor ions. In addition, adduct precursor ions (Na, K,...) also do not fragment well which leaves many potential hits unexploited. This calls for alternative ionization approaches and additional fragmentation techniques such as photodissociation (PD) or electron induced dissociation (EID). As the analysis needs to be keep short and sample is limited, multimodal approaches are becoming essential to gain as much as possible qualitative and quantitative information in a single LC-MS run. Recent instrumental improvements in high-resolution mass spectrometry (HRMS) have enabled data independent information acquisition (DIA) schemes, such as SWATH . With SWATH a collision induced dissociation MS/MS spectra can be generated for every precursor ion. Comparison with MS/MS database or the use of in-silico fragmentation tools can further improve compound identification, but improved selectivity and MS/MS information is needed. Implementing differential mobility spectrometry (DMS) for multidimensionnal separations (LCxDMS/DMS or SFCxDMS/MS) into the analytical workflow as the use of electron induced dissociation (EID), can significantly improve the performance of the analysis on singly charged precursor ions including adducts and multimers. Furthermore, under specific conditions atmospheric pressure ionization with micro-LC enables the selective generation either protonated molecules or radical cations. As for EID, radical fragmentation is of high interest as it opens the use of electron impact libraires for compound ID in LC-MS.
 R. Bonner, G. Hopfgartner, TrAC - Trends Anal. Chem. 120 (2019) 115278; https://doi.org/10.1016/j.trac.2018.10.014.