Major urinary metabolites of 6-keto-prostaglandin F2α in mice

J Lipid Res. 2013 Jul;54(7):1906-14. doi: 10.1194/jlr.M037192. Epub 2013 May 3.


Western diets are enriched in omega-6 vs. omega-3 fatty acids, and a shift in this balance toward omega-3 fatty acids may have health benefits. There is limited information about the catabolism of 3-series prostaglandins (PG) formed from eicosapentaenoic acid (EPA), a fish oil omega-3 fatty acid that becomes elevated in tissues following fish oil consumption. Quantification of appropriate urinary 3-series PG metabolites could be used for noninvasive measurement of omega-3 fatty acid tone. Here we describe the preparation of tritium- and deuterium-labeled 6-keto-PGF2α and their use in identifying urinary metabolites in mice using LC-MS/MS. The major 6-keto-PGF2α urinary metabolites included dinor-6-keto-PGF2α (~10%) and dinor-13,14-dihydro-6,15-diketo-PGF1α (~10%). These metabolites can arise only from the enzymatic conversion of EPA to the 3-series PGH endoperoxide by cyclooxygenases, then PGI3 by prostacyclin synthase and, finally, nonenzymatic hydrolysis to 6-keto-PGF2α. The 6-keto-PGF derivatives are not formed by free radical mechanisms that generate isoprostanes, and thus, these metabolites provide an unbiased marker for utilization of EPA by cyclooxygenases.

Keywords: cyclooxygenase; eicosapentaenoic acid; fish oil; prostacyclin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chromatography, Liquid
  • Deuterium / chemistry
  • Dinoprost / chemistry
  • Dinoprost / metabolism*
  • Dinoprost / urine
  • Humans
  • Isotope Labeling
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Tandem Mass Spectrometry
  • Tritium / chemistry


  • 6-keto-prostaglandin F2alpha
  • Tritium
  • Deuterium
  • Dinoprost