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LC-MS-Based Metabolomics of Biofluids Using All-Ion Fragmentation (AIF) Acquisition

  • Romanas Chaleckis
  • Shama Naz
  • Isabel Meister
  • Craig E. WheelockEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1730)

Abstract

The field of liquid chromatography-mass spectrometry (LC-MS)-based nontargeted metabolomics has advanced significantly and can provide information on thousands of compounds in biological samples. However, compound identification remains a major challenge, which is crucial in interpreting the biological function of metabolites. Herein, we present a LC-MS method using the all-ion fragmentation (AIF) approach in combination with a data processing method using an in-house spectral library. For the purposes of increasing accuracy in metabolite annotation, up to four criteria are used: (1) accurate mass, (2) retention time, (3) MS/MS fragments, and (4) product/precursor ion ratios. The relative standard deviation between ion ratios of a metabolite in a biofluid vs. its analytical standard is used as an additional metric for confirming metabolite identity. Furthermore, we include a scheme to distinguish co-eluting isobaric compounds. Our method enables database-dependent targeted as well as nontargeted metabolomics analysis from the same data acquisition, while simultaneously improving the accuracy in metabolite identification to increase the quality of the resulting biological information.

Key words

Metabolomics Liquid chromatography-mass spectrometry (LC-MS) All-ion fragmentation (AIF) Metabolite annotation 

Abbreviations

ACN

Acetonitrile

AIF

All-ion fragmentation

AM

Accurate mass

CID

Collision-induced dissociation

EIC

Extracted ion chromatogram

HILIC

Hydrophilic interaction liquid chromatography

LC-MS

Liquid chromatography-mass spectrometry

MeOH

Methanol

RP

Reverse phase

RT

Retention time

Notes

Acknowledgments

We acknowledge the support of the Swedish Heart Lung Foundation (HLF 20140469), the Swedish Research Council (2016-02798), the Swedish Foundation for Strategic Research, the Karolinska Institutet and AstraZeneca Joint Research Program in Translational Science (ChAMP; Centre for Allergy Research Highlights Asthma Markers of Phenotype), the Novo Nordisk Foundation (TrIC NNF15CC0018486 and MSAM NNF15CC0018346), and Gunma University Initiative for Advanced Research (GIAR). This work was supported in part by The Environment Research and Technology Development Fund (ERTDF) (Grant No 5-1752). CEW was supported by the Swedish Heart Lung Foundation (HLF 20150640).

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Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  • Romanas Chaleckis
    • 1
    • 2
  • Shama Naz
    • 1
  • Isabel Meister
    • 1
    • 2
  • Craig E. Wheelock
    • 1
    • 2
    Email author
  1. 1.Division of Physiological Chemistry 2, Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSweden
  2. 2.Gunma University Initiative for Advanced Research (GIAR), Gunma UniversityGunmaJapan

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