Quantitative method for the profiling of the endocannabinoid metabolome by LC-atmospheric pressure chemical ionization-MS.
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.
Williams
John
J
Center for Drug Discovery, Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA.
Wood
JodiAnne
J
Pandarinathan
Lakshmipathi
L
Karanian
David A
DA
Bahr
Ben A
BA
Vouros
Paul
P
Makriyannis
Alexandros
A
D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D001095:Arachidonic Acids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D001274:Atmospheric Pressure; D001923:Brain Chemistry; D063385:Cannabinoid Receptor Modulators / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005989:Glycerides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013997:Time Factors; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate; C078814:anandamide