Premium
Practical application of in silico fragmentation based residue screening with ion mobility high‐resolution mass spectrometry
Author(s) -
Kaufmann Anton,
Butcher Patrick,
Maden Kathry,
Walker Stephan,
Widmer Mirjam
Publication year - 2017
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.7890
Subject(s) - chemistry , ion mobility spectrometry , ion , mass spectrometry , fragmentation (computing) , analytical chemistry (journal) , in silico , chromatography , biochemistry , organic chemistry , computer science , gene , operating system
Rationale A screening concept for residues in complex matrices based on liquid chromatography coupled to ion mobility high‐resolution mass spectrometry LC/IMS‐HRMS is presented. The comprehensive four‐dimensional data (chromatographic retention time, drift time, mass‐to‐charge and ion abundance) obtained in data‐independent acquisition (DIA) mode was used for data mining. An in silico fragmenter utilizing a molecular structure database was used for suspect screening, instead of targeted screening with reference substances. Methods The utilized data‐independent acquisition mode relies on the MS E concept; where two constantly alternating HRMS scans (low and high fragmentation energy) are acquired. Peak deconvolution and drift time alignment of ions from the low (precursor ion) and high (product ion) energy scan result in relatively clean product ion spectra. A bond dissociation in silico fragmenter (MassFragment) supplied with mol files of compounds of interest was used to explain the observed product ions of each extracted candidate component (chromatographic peak). Results Two complex matrices (fish and bovine liver extract) were fortified with 98 veterinary drugs. Out of 98 screened compounds 94 could be detected with the in silico based screening approach. The high correlation among drift time and m/z value of equally charged ions was utilized for an orthogonal filtration (ranking). Such an orthogonal ion mobility based filter removes multiply charged ions (e.g. peptides and proteins from the matrix) as well as noise and artefacts. Most significantly, this filtration dramatically reduces false positive findings but hardly increases false negative findings. Conclusions The proposed screening approach may offer new possibilities for applications where reference compounds are hardly or not at all commercially available. Such areas may be the analysis of metabolites of drugs, pyrrolizidine alkaloids, marine toxins, derivatives of sildenafil or novel designer drugs (new psychoactive substances). Copyright © 2017 John Wiley & Sons, Ltd.