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Abstract
Untargeted metabolite profiling of biological samples is a challenge for analytical science due to the high degree of complexity of biofluids. Isobaric species may also not be resolved using mass spectrometry alone. As a result of these factors, many potential biomarkers may not be detected or are masked by co-eluting interferences in conventional LC-MS metabolomic analyses. In this study, a comprehensive liquid chromatography-mass spectrometry workflow incorporating a fast-scanning miniaturised high-field asymmetric waveform ion mobility spectrometry separation (LC-FAIMS-MS) is applied to the untargeted metabolomic analysis of human urine. The time-of-flight mass spectrometer used in the study was scanned at a rate of 20 scans s−1 enabling a FAIMS CF spectrum to be acquired within a 1-s scan time, maintaining an adequate number of data points across each LC peak. The developed method is demonstrated to be able to resolve co-eluting isomeric species and shows good reproducibility (%RSD < 4.9%). The nested datasets obtained for fresh, aged, and QC urine samples were submitted for multivariate statistical analysis. Seventy unique biomarker ions showing a statistically significant difference between fresh and aged urine were identified with optimal transmission CF values obtained across the full CF spectrum. The potential of using FAIMS to select ions for in-source collision-induced dissociation is demonstrated for FAIMS-selected methylxanthine ions yielding characteristic fragment ion species indicative of the precursor.Graphical abstract
Highlights
Metabolomic profiling remains a challenging task due the complexity of biological samples
We present a workflow for non-targeted metabolomic studies of urine samples by combining hydrophilic interaction liquid chromatography (HILIC) with fast-scanning miniaturised field asymmetric waveform ion mobility spectrometry (FAIMS) and time-of-flight mass spectrometry (TOFMS)
RSD% were below 5% for peak areas and below 0.2% for retention time, which is suitable for metabolomic applications, allowing the acquisition of nested LC-FAMS-MS data without increasing the liquid chromatography-mass spectrometry (LC-MS) run time
Summary
Metabolomic profiling remains a challenging task due the complexity of biological samples. Advanced Materials and Healthcare Technology Division, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK used in the metabolome composition analysis is liquid chromatography-mass spectrometry (LC-MS) [1,2,3]. Resolving isobaric species may not be achieved by mass spectrometry alone. These issues can be overcome by incorporating another separation technique such as ion mobility spectrometry (IMS) into the analysis. In this technique, ions in the gas phase are separated according to their mobility in an electric field [5]. The main advantage of IMS is its rapid time scale, so it is perfectly suited to be coupled to other separation and detection methods and there is growing interest in applying IMS to MS and LC-MS for investigating the composition of body fluids [6,7,8]
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