Synthesis of [13C4]-labeled ∆9-Tetrahydrocannabinol and 11-nor-9-Carboxy-∆9-tetrahydrocannabinol as Internal Standards for Reducing Ion Suppressing/Alteration Effects in LC/MS-MS Quantification

Abstract

(−)-∆9-Tetrahydrocannabinol is the principal psychoactive component of the cannabis plant and also the active ingredient in some prescribed drugs. To detect and control misuse and monitor administration in clinical settings, reference samples of the native drugs and their metabolites are needed. The accuracy of liquid chromatography/mass spectrometric quantification of drugs in biological samples depends among others on ion suppressing/alteration effects. Especially, 13 C-labeled drug analogues are useful for minimzing such interferences. Thus, to provide internal standards for more accurate quantification and for identification purpose, synthesis of [ tetrahydrocannabinol was shortened from three to two steps by employing nitromethane as a co-solvent in condensation with (+)-apoverbenone.

Synthesis of the Major Mammalian Metabolites of THCV

“…Additional experiments are now required to establish whether THCV metabolites can also interact with CB1 and CB2 receptors in vitro, in various tests of functional activity, and in vivo. The availability of synthesized THCV metabolites is therefore critical for the analysis of their biological actions, and, although some approaches have been reported − for their de novo synthesis, none of these have started from botanically derived, stereochemically pure THCV. Cannabinoids are sensitive to oxidative environments, and for this reason, the oxidized metabolites are often prepared by complex de novo syntheses that require expensive stereoselective reagents.…”