Journal
PROTEOMICS
Volume 20, Issue 11, Pages -Publisher
WILEY
DOI: 10.1002/pmic.201900070
Keywords
in-source fragmentation; ion suppression; isobaric; isomeric species; multidimensional mass spectrometry; shotgun lipidomics
Funding
- National Natural Science Foundation of China [81803861]
- National Key R&D Program of China [2018YFC1705500]
- NIH/NIA [RF1 AG061872]
- University of Texas Health Science Center at San Antonio (UT Health SA)
- Mass Spectrometry Core Facility of UT Health SA
- Methodist Hospital Foundation endowment
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Direct infusion-based shotgun lipidomics is one of the most powerful and useful tools in comprehensive analysis of lipid species from lipid extracts of various biological samples with high accuracy/precision. However, despite many advantages, the classical shotgun lipidomics suffers some general dogmas of limitations, such as ion suppression, ambiguous identification of isobaric/isomeric lipid species, and ion source-generated artifacts, restraining the applications in analysis of low-abundance lipid species, particularly those less ionizable or isomers that yield almost identical fragmentation patterns. This article reviews the strategies (such as modifier addition, prefractionation, chemical derivatization, charge feature utilization) that have been employed to improve/eliminate these limitations in modern shotgun lipidomics approaches (e.g., high mass resolution mass spectrometry-based and multidimensional mass spectrometry-based shotgun lipidomics). Therefore, with the enhancement of these strategies for shotgun lipidomics, comprehensive analysis of lipid species including isomeric/isobaric species is achieved in a more accurate and effective manner, greatly substantiating the aberrant lipid metabolism, signaling trafficking, and homeostasis under pathological conditions.
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