Application of differential mobility-mass spectrometry for untargeted human plasma metabolomic analysis

Anal Bioanal Chem. 2019 Sep;411(24):6297-6308. doi: 10.1007/s00216-019-01719-z. Epub 2019 Apr 2.


Differential mobility spectrometry (DMS) has been gaining popularity in small molecule analysis over the last few years due to its selectivity towards a variety of isomeric compounds. While DMS has been utilized in targeted liquid chromatography-mass spectrometry (LC-MS), its use in untargeted discovery workflows has not been systematically explored. In this contribution, we propose a novel workflow for untargeted metabolomics based solely on DMS separation in a clinically relevant chronic kidney disease (CKD) patient population. We analyzed ten plasma samples from early- and late-stage CKD patients. Peak finding, alignment, and filtering steps performed on the DMS-MS data yielded a list of 881 metabolic features (unique mass-to-charge and migration time combinations). Differential analysis by CKD patient group revealed three main features of interest. One of them was putatively identified as bilirubin based on high-accuracy MS data and comparison of its optimum compensation voltage (COV) with that of an authentic standard. The DMS-MS analysis was four times faster than a typical HPLC-MS run, which suggests a potential for the utilization of this technique in screening studies. However, its lower separation efficiency and reduced signal intensity make it less suitable for low-abundant features. Fewer features were detected by the DMS-based platform compared with an HPLC-MS-based approach, but importantly, the two approaches resulted in different features. This indicates a high degree of orthogonality between HPLC- and DMS-based approaches and demonstrates the need for larger studies comparing the two techniques. The workflow described here can be adapted for other areas of metabolomics and has a value as a prescreening method to develop semi-targeted workflows and as a faster alternative to HPLC in large biomedical studies.

Keywords: Biomarker discovery; Chronic kidney disease; Differential mobility spectrometry; Mass spectrometry; Untargeted metabolomics.

MeSH terms

  • Chromatography, High Pressure Liquid / methods
  • Cohort Studies
  • Glomerular Filtration Rate
  • Humans
  • Ion Mobility Spectrometry / methods*
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / physiopathology
  • Mass Spectrometry / methods*
  • Metabolomics*
  • Pilot Projects