Rapid HILIC-Z ion mobility mass spectrometry (RHIMMS) method for untargeted metabolomics of complex biological samples

Martina Pičmanová; Tessa Moses; Joan Cortada-Garcia; Georgina Barrett; Hannah Florance; Sufyan Pandor; Karl Burgess

doi:10.1007/s11306-022-01871-1

Rapid HILIC-Z ion mobility mass spectrometry (RHIMMS) method for untargeted metabolomics of complex biological samples

Metabolomics. 2022 Feb 28;18(3):16. doi: 10.1007/s11306-022-01871-1.

Authors

Martina Pičmanová¹, Tessa Moses², Joan Cortada-Garcia¹, Georgina Barrett¹, Hannah Florance³, Sufyan Pandor³, Karl Burgess^{4

5}

Affiliations

¹ Institute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh, Max Born Crescent, Edinburgh, EH9 3BF, UK.
² EdinOmics, University of Edinburgh, Max Born Crescent, Edinburgh, EH9 3BF, UK.
³ Agilent Technologies UK Limited, Cheadle Royal Business Park Stockport, Cheshire, SK8 3GR, UK.
⁴ Institute of Quantitative Biology, Biochemistry and Biotechnology, University of Edinburgh, Max Born Crescent, Edinburgh, EH9 3BF, UK. karl.burgess@ed.ac.uk.
⁵ EdinOmics, University of Edinburgh, Max Born Crescent, Edinburgh, EH9 3BF, UK. karl.burgess@ed.ac.uk.

Abstract

Introduction: Recent advances in high-throughput methodologies in the 'omics' and synthetic biology fields call for rapid and sensitive workflows in the metabolic phenotyping of complex biological samples.

Objective: The objective of this research was to evaluate a straightforward to implement LC-MS metabolomics method using a commercially available chromatography column that provides increased throughput. Reducing run time can potentially impact chromatography and therefore the effects of ion mobility spectrometry to expand peak capacity were also evaluated. Additional confidence provided via collision cross section measurements for detected features was also explored.

Methods: A rapid untargeted metabolomics workflow was developed with broad metabolome coverage, combining zwitterionic-phase hydrophilic interaction chromatography (HILIC-Z) with drift tube ion mobility-quadrupole time-of-flight (DTIM-qTOF) mass spectrometry. The analytical performance of our method was explored using extracts from complex biological samples, including a reproducibility study on chicken serum and a simple comparative study on a bacterial metabolome.

Results: The method is acronymised RHIMMS for rapid HILIC-Z ion mobility mass spectrometry. We present the RHIMMS workflow starting with data acquisition, followed by data processing and analysis. RHIMMS demonstrates improved chromatographic separation for a selection of metabolites with wide physicochemical properties while maintaining reproducibility at better than 20% over 200 injections at 3.5 min per sample for the selected metabolites, and a mean of 13.9% for the top 50 metabolites by intensity. Additionally, the combination of rapid chromatographic separation with ion mobility allows improved annotation and the ability to distinguish isobaric compounds.

Conclusion: Our results demonstrate RHIMMS to be a rapid, reproducible, sensitive and high-resolution analytical platform that is highly applicable to the untargeted metabolomics analysis of complex samples.

Keywords: HILIC; High throughput; Ion mobility; Untargeted metabolomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chromatography, Liquid / methods
Ion Mobility Spectrometry* / methods
Mass Spectrometry / methods
Metabolomics* / methods
Reproducibility of Results