Quantitative Method for the Profiling of the Endocannabinoid Metabolome by LC-Atmospheric Pressure Chemical Ionization-MS

• Published in: Analytical chemistry (Washington) 2007-08, Vol.79 (15), p.5582-5593
• Main Authors: Williams, John, Wood, JodiAnne, Pandarinathan, Lakshmipathi, Karanian, David A, Bahr, Ben A, Vouros, Paul, Makriyannis, Alexandros
• Format: Article
• Language: English
• Subjects: Amidohydrolases - antagonists & inhibitors; Analytical chemistry; Animals; Arachidonic Acids - analysis; Arachidonic Acids - chemistry; Arachidonic Acids - metabolism; Atmospheric Pressure; Brain Chemistry; Cannabinoid Receptor Modulators - analysis; Cannabinoid Receptor Modulators - chemistry; Cannabinoid Receptor Modulators - metabolism; Cerebral Cortex - chemistry; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Chemical compounds; Chemistry; Chromatographic methods and physical methods associated with chromatography; Chromatography, High Pressure Liquid - methods; Endocannabinoids; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Exact sciences and technology; Glycerides - analysis; Glycerides - chemistry; Glycerides - metabolism; Ion chromatography; Marijuana; Mass spectrometry; Other chromatographic methods; Polyunsaturated Alkamides - analysis; Polyunsaturated Alkamides - chemistry; Polyunsaturated Alkamides - metabolism; Rats; Reproducibility of Results; Spectrometric and optical methods; Spectrometry, Mass, Electrospray Ionization - methods; Time Factors
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/ac0624086

The endocannabinoid system's biological significance continues to grow as novel endocannabinoid metabolites are discovered. Accordingly, a myopic view of the system that focuses solely on one or two endocannabinoids, such as anandamide or 2-arachidonoyl glycerol, is insufficient to describe the biological responses to perturbations of the system. Rather, the endocannabinoid metabolome as a whole must be analyzed. The work described here is based on liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry. This method has been validated to quantify, in a single chromatographic run, the levels of 15 known or suspected metabolites of the endocannabinoid system in the rat brain and is applicable to other biological matrixes. We have obtained an endocannabinoid profile specifically for the frontal cortex of the rat brain and have determined anandamide level differences following the administration of the fatty acid amide hydrolase inhibitor AM374.