Distribution of free and conjugated cannabinoids in human bile samples

Marie Fabritius, Christian Staub, Patrice Mangin, Christian Giroud

Index: Forensic Sci. Int. 223(1-3) , 114-8, (2012)

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Abstract

The metabolism of Δ9-tetrahydrocannabinol (THC) is relatively complex, and over 80 metabolites have been identified [1]. However, much less is known about the formation and fate of cannabinoid conjugates. Bile excretion is known to be an important route for the elimination of phase II metabolites. A liquid chromatography–tandem mass spectrometry LC–MS/MS procedure for measuring cannabinoids in oral fluid was adapted, validated and applied to 10 bile samples. THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH), cannabinol (CBN), cannabidiol (CBD), Δ9-tetrahydrocannabinolic acid A (THC-A), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol glucuronide (THCCOOH-gluc) and Δ9-tetrahydrocannabinol glucuronide (THC-gluc) were determined following solid-phase extraction and LC–MS/MS. High concentrations of THCCOOH-gluc were found in bile samples (range: 139–21,275ng/mL). Relatively high levels of THCCOOH (7.7–1548ng/mL) and THC-gluc (38–1366ng/mL) were also measured. THC-A, the plant precursor of THC, was the only cannabinoid that was not detected. These results show that biliary excretion is an important route of elimination for cannabinoids conjugates and that their enterohepatic recirculation is a significant factor to consider when analyzing blood elimination profiles of cannabinoids. Furthermore, we suggest that the bile is the matrix of choice for the screening of phase II cannabinoid metabolites.