Author
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STRASSBURG, KATRIN - Leiden University |
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Pedersen, Theresa |
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HUIJBRECHTS, ANNEMARIE - University Medical Center - Utrecht |
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KORTEKAAS, KIRSTEN - Leiden University Medical Center |
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LINDEMAN, JAN - Leiden University Medical Center |
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DANE, ADRIE - Leiden University |
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BERGER, RUDD - University Medical Center - Utrecht |
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BRENKMAN, ARJAN - University Medical Center - Utrecht |
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HANKEMEIER, THOMAS - Leiden University |
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VAN DUYNHOVEN, JOHN - Leiden University |
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KALKHOVEN, ERIC - University Medical Center - Utrecht |
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Newman, John |
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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. |