Synthesis of 13C4-labeled ∆9-tetrahydrocannabinol and 11-nor-9-carboxy-∆9-tetrahydrocannabinol as internal standards for reducing ion suppressingalteration effects in LCMS-MS quantification.
(-)-∆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 chromatographymass spectrometric quantification of drugs in biological samples depends among others on ion suppressingalteration effects. Especially, 13C-labeled drug analogues are useful for minimzing such interferences. Thus, to provide internal standards for more accurate quantification and for identification purpose, synthesis of 13C4-∆9-tetrahydro-cannabinol and 13C4-11-nor-9-carboxy-∆9-tetrahydrocannabinol was developed via 13C4-olivetol. Starting from 13C4-olivetol the synthesis of 13C4-11-nor-9-carboxy-∆9-tetrahydrocannabinol was shortened from three to two steps by employing nitromethane as a co-solvent in condensation with ()-apoverbenone.