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. 2006 Oct 20;8(4):E655–E660. doi: 10.1208/aapsj080474

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

John Williams 1,2, Lakshmipathi Pandarinathan 1, Jodi Anne Wood 1, Paul Vouros 2, Alexandros Makriyannis 1,
PMCID: PMC2751361  PMID: 17233529

Abstract

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.

Keywords: fatty acids, LC-MS, metabolome, oxazoline derivatives, microwave synthesis

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