An Untargeted Lipidomics Workflow Incorporating High-Resolution Demultiplexing (HRdm) Drift Tube Ion Mobility-Mass...

Area of Science:

• Analytical Chemistry
• Metabolomics
• Biochemistry

Background:

• Lipidomics faces challenges in separating lipid isomers, hindering the understanding of metabolic disorders.
• High-resolution ion mobility (HRIM) strategies improve isomer separation in liquid chromatography-mass spectrometry (LC-MS).

Purpose of the Study:

• To demonstrate the utility of high-resolution demultiplexing (HRdm) in untargeted lipidomic analysis.
• To investigate lipid profiles in ATP10D dysfunctional murine models using HRdm.

Main Methods:

• Incorporation of HRdm, a high-resolution demultiplexing strategy using multiplexed drift tube ion mobility spectrometry (DTIMS).
• Application of HRdm-LC-MS untargeted lipidomic pipelines to murine models.
• Post-acquisition algorithmic deconvolution for high ion mobility resolution.

Main Results:

• HRdm increased total lipid features by 2.5-fold compared to standard demultiplexed DTIMS due to enhanced isomer resolution.
• HRdm resolved isomeric lipids, such as PC 36:5, which were significantly higher in dysfunctional ATP10D mice.
• Specific lipid isomers were identified by HRdm that were undetectable by standard DTIMS.

Conclusions:

• HRdm significantly improves the resolution of isomeric lipids in untargeted lipidomics.
• This technique enhances the analytical understanding of lipids in disease complexity and biological studies.
• HRdm offers potential for more accurate lipid biomarker discovery in metabolic disorders.