A commercial liquid chromatography/drift tube ion mobility-mass spectrometer (LC/IM-MS) was evaluated for its utility in global metabolomics analysis. Performance was assessed using 12 targeted metabolite standards where the limit of detection (LOD), linear dynamic range, resolving power, and collision cross section (Ω) are reported for each standard. Data were collected in three different instrument operation modes: flow injection analysis with IM-MS (FIA/IM-MS), LC/MS, and LC/IM-MS. Metabolomics analyses of human plasma and HaCaT cells were used to compare the above three operation modes. LC/MS provides linearity in response, data processing automation, improved limits of detection, and ease of use. Advantages of LC/IM-MS and FIA/IM-MS include the ability to develop mobility-mass trend lines for structurally similar biomolecules, increased peak capacity, reduction of chemical/matrix noise, improvement in signal-to-noise, and separations of isobar/isomer compounds that are not resolved by LC. We further tested the feasibility of incorporating IM-MS into conventional LC/MS metabolomics workflows. In general, the addition of ion mobility dimension has increased the separation of compounds in complex biological matrixes and has the potential to largely improve the throughput of metabolomics analysis.
Bibliographical noteFunding Information:
This work was supported by the DARPA award 13-34-RTA-FP- 007 to William Old (N. Reisdorph, subcontractor). The opinions, points of view, findings, and conclusions or recommendations expressed in this publication represent a consensus of the authors and do not necessarily represent the official position or policies of the U.S. Department of Defense. Any products and manufacturers discussed are presented for informational purposes only and do not constitute product approval or endorsement by the U.S. Department of Defense.
© 2017 American Chemical Society.