title: 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid ethyl ester (THC-COOEt): unsuccessful search for a marker of combined cannabis and alcohol consumption.
abstract: 11-Nor-Delta(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.
authors.affiliation: Institute of Legal Medicine, University Hospital Charité, Hittorfstr. 18, 14195 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nadulski
authors.forename: Simona
authors.initials: S
authors.lastname: Bleeck
authors.forename: Johannes
authors.initials: J
authors.lastname: Schräder
authors.forename: Wolf-Rainer
authors.initials: WR
authors.lastname: Bork
authors.forename: Fritz
authors.initials: F
authors.lastname: Pragst
mesh_terms: D000428:Alcohol Drinking; D000437:Alcoholism / Q000175:diagnosis; D015415:Biomarkers / Q000032:analysis; D002492:Central Nervous System Depressants / Q000097:blood; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000032:analysis; D000431:Ethanol / Q000097:blood; D005227:Fatty Acids / Q000032:analysis; D053593:Forensic Toxicology / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry; D006197:Hair / Q000737:chemistry; D006213:Hallucinogens / Q000032:analysis*; D006801:Humans; D008385:Marijuana Smoking; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D015415:Biomarkers; D002492:Central Nervous System Depressants; D005227:Fatty Acids; D006213:Hallucinogens; D000431:Ethanol; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol