Taken

together, these data suggest that CYP1A1- and 1B1-mediated arachidonic acid metabolism can produce significant quantities of EETs in addition to the widely recognized CYPs of the 2 family. 6. Summary and Future Directions Targeted chiral LC-SRM/MS analysis of arachidonic acid metabolites has until recently been performed primarily by ECAPCI methodology [105]. This requires derivatization to PFB-derivatives and the use of normal phase chromatography, which has severely restricted its utility. Nevertheless significant Inhibitors,research,lifescience,medical progress has been made in monitoring the formation of chiral eicosanoids that result from COX-, LOX-, and CYP-mediated arachidonic acid metabolism. The recent development of chiral reversed-phase Inhibitors,research,lifescience,medical methodology promises to make targeted approaches more readily available to other researchers in the field [93]. However, the need for rigorous attention to detail and the requirement for heavy isotope internal standards [149] to ensure specificity, means that it will be difficult to extend these approaches to more global analyses. The Inhibitors,research,lifescience,medical recent identification of the N-arachidonyl-amino acid derivatives of glutamic acid and glutamine [150] as significant metabolites in rat brain and the previous identification N-arachidonyl-glycine, alanine, and dopamine [151,152] will also require the use of chiral LC-MS methodology in order to ensure that no racemization

of the relevant amino acids has occurred. Similar methodology will also be required for other polyunsaturated Inhibitors,research,lifescience,medical fatty acid derivatives of amino acids such as N-docosahexaenoyl-glutamic acid [150]. As more sophisticated instruments become more widely available, it will be possible to increase specificity of analysis through the use of multiple transitions that are employed in multiple reaction monitoring (MRM) methodology [149]. This will enable several MRM transitions to be employed for qualifying

the Inhibitors,research,lifescience,medical analyte and another transition to be employed for quantification as we described recently in our serum proteomics studies [153]. Furthermore, new high-resolution LC-SRM/MS methodology and is becoming more amenable to high throughput applications. The use of high resolution LC-MS will confer additional much needed specificity for difficult eicosanoid analyses in complex biological fluids such as urine. Acknowledgments This work was supported by NIH grants U01ES016004, R01CA130961, and P30ES013508. selleck conflict of Interest Conflict of Interest The authors declare no conflict of interest.
Lipidomic profiling methods reflect the lipid status of a phenotype at a particular time point [1,2,3] and are therefore valuable tools to improve the understanding the biological roles of lipids. Unlike genes or proteins, the lipid composition can rapidly be influenced by external factors like nutrition or environmental conditions and is alterable even within seconds [2,3,4,5].