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

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.