11-Nor-Δ 9-tetrahydrocannabinol-9-carboxylic acid ethyl ester (THC-COOEt): Unsuccessful search for a marker of combined cannabis and alcohol consumption

Abstract

11-Nor-Δ 9-tetrahydrocannabinol-9-carboxylic acid ethyl ester (THC-COOEt) can be presumed to be a mixed metabolite formed during combined consumption of cannabinoids and alcohol. In order to examine this hypothesis, THC-COOEt and its deuterated analogue D 3-THC-COOEt were synthesized as reference substance and internal standard from the corresponding carboxylic acids and diazoethane and methods were developed for the sensitive detection of THC-COOEt in plasma and hair based on gas chromatography–electron impact mass spectrometry after silylation with N-methyl- N-tert-butyldimethylsilyl-trifluoroacetamide and gas chromatography–negative chemical ionization mass spectrometry (GC-NCI-MS) as well as tandem mass spectrometry (GC-NCI-MS-MS) after derivatization with pentafluoropropionyl anhydride. The methods were applied for THC-COOEt determination to plasma samples from 22 drunk driving cases which contained both ethanol (0.30–2.16 mg/g) and THC-COOH (15–252 ng/mL) as well as to 12 hair samples from drug fatalities which were both positive for THC (0.09–2.04 ng/mg) and fatty acid ethyl esters as markers of chronic alcohol abuse (0.70–6.3 ng/mg). In none of these samples THC-COOEt could be found with limits of detection of 0.3 ng/mL in plasma and 2 pg/mg in hair in 11 samples using GC-NCI-MS and 0.2 pg/mg in one sample using GC-NCI-MS. Therefore, the use of this compound as a marker for combined cannabis and alcohol consumption could not be achieved.