The AAPS Journal

, Volume 8, Issue 4, pp E655–E660 | Cite as

Endocannabinoid metabolomics: A novel liquid chromatography-mass spectrometry reagent for fatty acid analysis

  • John Williams
  • Lakshmipathi Pandarinathan
  • Jodi Anne Wood
  • Paul Vouros
  • Alexandros Makriyannis


We have synthesized 4,4-dimethoxyoxazoline derivatives of several fatty acids associated with the endocannabinoid metabolome using tris(hydroxymethyl)aminomethane in a 1-step reaction by microwave irradiation. The derivatization incorporates a nitrogen into the final product, which allows for improved detection by liquid chromatographymass spectrometry in positive atmospheric pressure chemical ionization (APCI) mode. Palmitic and oleic acid derivatives show a 200-fold increase in sensitivity compared with the free acids when analyzed in negative-mode APCI. In addition to improving sensitivity, the oxazoline derivatization creates a similar ionization response for the fatty acids tested, which simplifies their quantitation. Fatty acid oxazoline derivatives can be detected using the same conditions optimized for the endocannabinoids, which allows for a simultaneous quantitation of the entire endocannabinoid metabolome.


fatty acids LC-MS metabolome oxazoline derivatives microwave synthesis 


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Copyright information

© American Association of Pharmaceutical Scientists 2006

Authors and Affiliations

  • John Williams
    • 1
    • 2
  • Lakshmipathi Pandarinathan
    • 1
  • Jodi Anne Wood
    • 1
  • Paul Vouros
    • 2
  • Alexandros Makriyannis
    • 1
  1. 1.Center for Drug DiscoveryNortheastern UniversityBoston
  2. 2.Barnett Institute and Department of ChemistryNortheastern UniversityBoston

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