A CREMONESI¹, M HERSBERGER¹, M HERSBERGER<sup>2

1</sup>Division of Clinical Chemistry and Biochemistry, Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland, ²Zurich Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

Lipid mediators play an important role during the development, maintenance and resolution of inflammation. They are derived either from arachidonic acid (AA) or from the essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and they can be subdivided according to their pro- or anti-inflammatory functions. Pro-inflammatory lipid mediators like prostaglandins and leukotrienes are derived from the common precursor AA. Anti-inflammatory and pro-resolving lipid mediators include metabolites of AA, such as lipoxins A4 and B4, DHA derivatives like D-series resolvins, protectins and maresins, and the E-series of resolvins derived from EPA.

In light of their importance in the regulation of the inflammatory response, we set out to accurately measure the concentrations of these lipid mediators in plasma. However, these compounds are analytically challenging because of (1) their structural similarities, (2) their relative hydrophobicity and poor ionization efficiency, (3) their chemical instability both in plasma as well as in organic solutions and (4) because of their low abundance in blood. In order to measure these compounds in an accurate and precise way, a solid phase extraction method was developed to extract 24 different lipid mediators with an extraction yield of >70%. In order to maximize the chromatographic separation, extracts were separated by UPLC and further analyzed by high-resolution mass spectrometry on a Q-Exactive (Thermo Fisher Scientific). Data will be presented about the performance of the established LC-MS/MS method and its potential clinical applications.