Maximizing Lipidome Coverage of Mouse Liver Following the IV Administration of Gefitinib by Combining Both UHPLC-MS-Based Untargeted and Targeted Lipidomics

High Resolution Image Download MS PowerPoint Slide 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.