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Title:   Author  item
                                            STRASSBURG, KATRIN - Leiden Universityitem
                                            Pedersen, Theresaitem
                                            HUIJBRECHTS, ANNEMARIE - University Medical Center - Utrechtitem
                                            KORTEKAAS, KIRSTEN - Leiden University Medical Centeritem
                                            LINDEMAN, JAN - Leiden University Medical Centeritem
                                            DANE, ADRIE - Leiden Universityitem
                                            BERGER, RUDD - University Medical Center - Utrechtitem
                                            BRENKMAN, ARJAN - University Medical Center - Utrechtitem
                                            HANKEMEIER, THOMAS - Leiden Universityitem
                                            VAN DUYNHOVEN, JOHN - Leiden Universityitem
                                            KALKHOVEN, ERIC - University Medical Center - Utrechtitem
                                            Newman, Johnitem
                                            VREEKEN, ROB - Leiden University
  Submitted to: Analytical and Bioanalytical Chemistry
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/14/2012
                                    Publication  Date: 7/20/2012
                                    Citation: Strassburg, K., Pedersen, T.L., Huijbrechts, A.M., Kortekaas, K., Lindeman, J., Dane, A., Berger, R., Brenkman, A., Hankemeier, T., Van Duynhoven, J., Kalkhoven, E., Newman, J.W., Vreeken, R. 2012. Quantitative profiling of oxylipins through comprehensive lc-ms/ms analysis: Application in cardiac surgery. Analytical and Bioanalytical Chemistry. 404(5):1413-1426.Interpretive Summary: Oxylipins, including eicosanoids, affect a broad range of biological processes, such as the initiation and resolution of inflammation. These compounds, also referred to as lipid mediators, are (non-) enzymatically generated by oxidation of polyunsaturated fatty acids such as arachidonic acid (AA). A plethora of lipid-mediators exist which makes the development of generic analytical methods challenging. Here we developed a robust and sensitive targeted analysis platform for oxylipins and applied it in a biological setting, using high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) operated in dynamic multiple reaction monitoring (dMRM). Besides the well- described AA metabolites, oxylipins derived from linoleic acid, dihomo-'-linolenic acid, a-linoleic acid, eicosapentaenoic acid and docosahexaenoic acid were included. Our comprehensive platform allows the quantitative evaluation of approximately 100 oxylipins down to low nanomolar levels. Applicability of the analytical platform was demonstrated by analyzing plasma samples of patients undergoing cardiac surgery. Altered levels of some of the oxylipins, especially in certain monohydroxy fatty acids such as 12-HETE and 12-HEPE, were observed in samples collected before and 24 hours after cardiac surgery. These findings indicate that this generic oxylipin profiling platform may be applied broadly to study these highly bioactive compounds in human disease.
                                Technical Abstract: Oxylipins, including eicosanoids, affect a broad range of biological processes, such as the initiation and resolution of inflammation. These compounds, also referred to as lipid mediators, are (non-) enzymatically generated by oxidation of polyunsaturated fatty acids such as arachidonic acid (AA). A plethora of lipid-mediators exist which makes the development of generic analytical methods challenging. Here we developed a robust and sensitive targeted analysis platform for oxylipins and applied it in a biological setting, using high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) operated in dynamic multiple reaction monitoring (dMRM). Besides the well- described AA metabolites, oxylipins derived from linoleic acid, dihomo-'-linolenic acid, a-linoleic acid, eicosapentaenoic acid and docosahexaenoic acid were included. Our comprehensive platform allows the quantitative evaluation of approximately 100 oxylipins down to low nanomolar levels. Applicability of the analytical platform was demonstrated by analyzing plasma samples of patients undergoing cardiac surgery. Altered levels of some of the oxylipins, especially in certain monohydroxy fatty acids such as 12-HETE and 12-HEPE, were observed in samples collected before and 24 hours after cardiac surgery. These findings indicate that this generic oxylipin profiling platform may be applied broadly to study these highly bioactive compounds in human disease.


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