Synthesis of [13C4]-labeled ∆9-tetrahydrocannabinol and 11-nor-9-carboxy-∆9-tetrahydrocannabinol as internal standards for reducing ion supressing/alteration effects in LC/MS-MS quantification

摘要

(−)-Δ9-Tetrahydrocannabinol is the principal psychoactive component of thecannabis plant and also the active ingredient in some prescribed drugs. To detect andcontrol misuse and monitor administration in clinical settings, reference samplesof the native drugs and their metabolites are needed. The accuracy of liquidchromatography/mass spectrometric quantification of drugs in biological samples dependsamong others on ion suppressing/alteration effects. Especially, 13C-labeled drug analoguesare useful for minimzing such interferences. Thus, to provide internal standards for moreaccurate quantification and for identification purpose, synthesis of [13C4]-Δ9-tetrahydrocannabinoland [13C4]-11-nor-9-carboxy-Δ9-tetrahydrocannabinol was developed via[13C4]-olivetol. Starting from [13C4]-olivetol the synthesis of [13C4]-11-nor-9-carboxy-Δ9-tetrahydrocannabinol was shortened from three to two steps by employing nitromethane as aco-solvent in condensation with (+)-apoverbenone.