Analysis of Tetrahydrocannabinol and its Metabolite, 11-Nor-9-Tetrahydrocannabinol-9-Carboxylic Acid, in Oral Fluid using Liquid Chromatography with Tandem Mass Spectrometry

This paper describes the determination of tetrahydrocannabinol (THC) and its metabolite, 11-nor-(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in oral fluid using solid-phase extraction and liquid chromatography with tandem mass spectral detection (LCMS-MS) and its application to proficiency specimens. The method employs collection of oral fluid with the Quantisal device, base hydrolysis, solid-phase extraction and LCMS-MS in positive ion electrospray mode. Because the concentration of the metabolite in oral fluid is quite low, extremely sensitive analytical methods are necessary. The requisite sensitivity was achieved by a simple, rapid derivatization of the compound after extraction. The derivatization conditions did not affect parent THC. The method was fully validated using standard parameters including linearity, sensitivity, accuracy, intra-day and inter-day imprecision, drug recovery from the collection pad, limit of quantitation, limit of detection and matrix effects. The procedure was applied to oral fluid proficiency specimens previously analyzed to assess the stability of THC-COOH.