Quantification of Endocannabinoids from Biological Samples Using Liquid Chromatography–Tandem Mass Spectrometry

Endocannabinoids (eCBs) are a family of lipid molecules with important regulatory function in the brain and immune system. The two well-studied eCBs are arachidonic acid derivatives, N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). Currently one of the most important methods for quantitative analysis of eCBs and related lipids from biological matrices is liquid chromatographic separation coupled with tandem mass spectroscopy (LC-MS/MS) owing to its high sensitivity and selectivity, as well as no derivatization procedures needed. Here we describe pretreatment procedures using solid-phase extraction for tissue sampling and an in vivo brain microdialysis approach prior to LC-MS/MS analysis, followed by detailed steps of LC-MS/MS analytic method to demonstrate the potential and application of this method in quantification of eCBs and congeners from various biological matrices.