Comprehensive lipidomic workflow for multicohort population phenotyping using stable isotope dilution targeted liquid chromatography-mass spectrometry
Author(s)
Type
Journal Article
Abstract
Dysregulated lipid metabolism underpins many chronic diseases including cardiometabolic diseases. Mass spectrometry-based lipidomics is an important tool for understanding mechanisms of lipid dysfunction and is widely applied in epidemiology and clinical studies. With ever-increasing sample numbers, single batch acquisition is often unfeasible, requiring advanced methods that are accurate and robust to batch-to-batch and interday analytical variation. Herein, an optimized comprehensive targeted workflow for plasma and serum lipid quantification is presented, combining stable isotope internal standard dilution, automated sample preparation, and ultrahigh performance liquid chromatography-tandem mass spectrometry with rapid polarity switching to target 1163 lipid species spanning 20 subclasses. The resultant method is robust to common sources of analytical variation including blood collection tubes, hemolysis, freeze–thaw cycles, storage stability, analyte extraction technique, interinstrument variation, and batch-to-batch variation with 820 lipids reporting a relative standard deviation of <30% in 1048 replicate quality control plasma samples acquired across 16 independent batches (total injection count = 6142). However, sample hemolysis of ≥0.4% impacted lipid concentrations, specifically for phosphatidylethanolamines (PEs). Low interinstrument variability across two identical LC-MS systems indicated feasibility for intra/inter-lab parallelization of the assay. In summary, we have optimized a comprehensive lipidomic protocol to support rigorous analysis for large-scale, multibatch applications in precision medicine. The mass spectrometry lipidomics data have been deposited to massIVE: data set identifiers MSV000090952 and 10.25345/C5NP1WQ4S.
Date Issued
2023-05-05
Date Acceptance
2023-02-01
Citation
Journal of Proteome Research, 2023, 22 (5), pp.1419-1433
ISSN
1535-3893
Publisher
American Chemical Society
Start Page
1419
End Page
1433
Journal / Book Title
Journal of Proteome Research
Volume
22
Issue
5
Copyright Statement
Copyright © 2023 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY-NC-ND 4.0 .
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000964359000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
Biochemical Research Methods
Biochemistry & Molecular Biology
DISCOVERY
HIGH-THROUGHPUT
IDENTIFICATION
LC-MS
Life Sciences & Biomedicine
lipid profiling
lipid quantification
lipidomics
lipids
liquid chromatography-mass spectrometry
metabolic phenotyping
molecular epidemiology
PLASMA
PROFILE
Science & Technology
SHOTGUN LIPIDOMICS
STABILITY
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2023-02-24