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Updated: May 18, 2026

Shotgun Lipidomics of Rodent Tissues
Published on: November 18, 2022
Online nanoscale ERLIC-MS outperforms RPLC-MS for shotgun proteomics in complex mixtures
Ebbing P de Jong1, Timothy J Griffin
1Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, United States.
Abstract:
We have explored the use of electrostatic repulsion hydrophilic interaction chromatography (ERLIC) as an alternative to the gold-standard in shotgun proteomics: reversed-phase (RP) LC for online ESI-MS/MS. Conditions for sample solubilization and initial gradient conditions were optimized to strike a balance between peptide solubility and maximum peptide retention when using mobile phase with high organic solvent concentration. Online ERLIC-MS demonstrated a 57% increase in total peptide identifications compared to RP-MS. We examined the mechanism of this improved performance and found that it stems from ERLIC's propensity to retain longer peptides, which can be identified with greater confidence. Online nanoscale ERLIC-MS provides a powerful new tool for enhancing MS-based shotgun proteomic in a broad range of applications.
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