A method based on catalytic hydrogenation for the identification of monohydroxy metabolites of isomeric tetrahydrocannabinols

Abstract

AbstractIdentification of isomeric monohydroxy metabolites of 6a,10a‐trans‐tetrahydrocannabinols (THCs) by gas chromatography/mass spectrometry as their trimethylsilyl derivatives is aided by catalytic hydrogenation to hydroxyhexahydrocannabinols (hydroxy‐HHCs) in cases where the metabolites themselves give similar spectra. This method gives common products from a range of hydroxy metabolites of isomeric‐THCs which can be compared with reference compounds synthesized from available hydroxy‐THCs from the Δ8 and Δ9‐series. Sufficient of these compounds are available to enable hydroxy‐HHCs to be prepared with hydroxy groups in most positions accessible to metabolic enzymes. This technique provides a simple alternative to a laborious synthesis of each new metabolite for confirmatory purposes and enables all metabolites in a metabolic experiment to be identified in a single sample. Catalytic hydrogenation was achieved using rhodium on alumina in methanol; this gave rapid, quantitative hydrogenation of underivatized metabolites without the elimination of the hydroxy groups inherent with hydrogenation with other common catalysts. The method was validated by an examination of the metabolites of Δ11 THC in rats and comparison of the results with published work.