Related Experiment Video
Updated: Jun 16, 2026
Shotgun Lipidomics of Rodent Tissues
Published on: November 18, 2022
Maximizing Lipidome Coverage of Mouse Liver Following the IV Administration of Gefitinib by Combining Both
Robert S Plumb1,2, Nyasha Munjoma3, Lee A Gethings3
1Waters Corporation, 34 Maple St, Milford, Massachusetts 01757, United States.
Abstract:
Both untargeted "discovery" and targeted lipid analyses were performed on liver extracts obtained from mice, following the intravenous administration (10 mg/kg) of the tyrosine kinase inhibitor gefitinib, to maximize coverage of the liver lipidome. Untargeted lipid analysis by RP-UHPLC-IM-MS in both +ve and -ve ESI showed time-related changes in lipid profiles, including reductions in the abundances of PCs and PEs and a concomitant rise in the LPCs. Targeted analysis by HILIC-UHPLC-MS using +ve ESI also showed time-related effects on the lipid profiles of gefitinib-dosed mice with PCs, SMs, TGs, and LPCs, particularly for the lipids PC(34:1), PC(32:1), SM(40:1), TG(48:1), and PC(32:0), and effects on a number of acyl carnitines were also noted. In addition, time-related effects were seen using -ve ESI on a range of lipids, including PGs, PCs, LPEs, PEs, and FFAs. The resulting data suggest widespread effects on fatty acid utilization and metabolism may occur in the liver of mice as a result of exposure to gefitinib.
Insights
Gefitinib treatment alters liver lipid profiles in mice, affecting fatty acid metabolism. Researchers observed significant changes in lipid abundances, suggesting widespread metabolic disruption.
Area of Science:
- Biochemistry
- Pharmacology
- Metabolomics
Background:
- Tyrosine kinase inhibitors like gefitinib are used in cancer therapy.
- Understanding drug-induced metabolic changes is crucial for patient safety and efficacy.
Purpose of the Study:
- To comprehensively analyze the impact of gefitinib on the mouse liver lipidome.
- To identify specific lipids and metabolic pathways affected by gefitinib exposure.
Main Methods:
- Liver extracts from gefitinib-treated mice were analyzed using untargeted and targeted lipidomics.
- Techniques included RP-UHPLC-IM-MS and HILIC-UHPLC-MS with both positive and negative electrospray ionization (ESI).
Main Results:
- Gefitinib administration led to time-dependent alterations in various lipid classes, including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), lysophosphatidylcholines (LPCs), sphingomyelins (SMs), and triglycerides (TGs).
- Specific lipids like PC(34:1), PC(32:1), SM(40:1), and TG(48:1) showed notable changes.
- Effects on acyl carnitines, prostaglandins (PGs), lysophosphatidylethanolamines (LPEs), and free fatty acids (FFAs) were also observed.
Conclusions:
- Gefitinib exposure induces significant and widespread changes in liver lipid metabolism in mice.
- These findings suggest potential disruptions in fatty acid utilization and overall hepatic metabolic homeostasis.
