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Plasma and urine profiles of Δ9-tetrahydrocannabinol and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes

Brenneisen, Rudolf ; Meyer, Pascale ; Chtioui, Haithem ; Saugy, Martial ; Kamber, Matthias

In: Analytical and Bioanalytical Chemistry, 2010, vol. 396, no. 7, p. 2493-2502

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    Titre
    • Plasma and urine profiles of Δ9-tetrahydrocannabinol and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes
    Auteur
    • Brenneisen, Rudolf. Department of Clinical Research, University of Berne, Murtenstr. 35, 3010, Berne, Switzerland
    • Meyer, Pascale. Department of Clinical Research, University of Berne, Murtenstr. 35, 3010, Berne, Switzerland
    • Chtioui, Haithem. Clinical Investigation Unit, University Hospital of Berne, 3010, Berne, Switzerland
    • Saugy, Martial. Swiss Laboratory for Doping Analyses, 1066, Epalinges, Switzerland
    • Kamber, Matthias. Antidoping Switzerland, P.O. Box606, 3000, Berne 22, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Analytical and Bioanalytical Chemistry, 2010, vol. 396, no. 7, p. 2493-2502. Springer-Verlag
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:316289
    Summary
    Since 2004, cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In doping urine analysis, the target analyte is 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), the cutoff being 15ng/mL. However, the wide urinary detection window of the long-term metabolite of Δ9-tetrahydrocannabinol (THC) does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance. The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70mg THC per cigarette. Plasma and urine were collected up to 8h and 11days, respectively. Total THC, 11-hydroxy-Δ9-tetrahydrocannabinol (THC-OH), and THC-COOH were determined after hydrolysis followed by solid-phase extraction and gas chromatography/mass spectrometry. The limits of quantitation were 0.1-1.0ng/mL. Eight puffs delivered a mean THC dose of 45mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2-59.1, 0.1-3.9, and 0.4-16.4ng/mL, respectively. Peak concentrations were observed at 5, 5-20, and 20-180min. Urine levels were measured in the ranges 0.1-1.3, 0.1-14.4, and 0.5-38.2ng/mL, peaking at 2, 2, and 6-24h, respectively. The times of the last detectable levels were 2-8, 6-96, and 48-120h. Besides high to very high THC-COOH levels (245 ± 1,111ng/mL), THC (3 ± 8ng/mL) and THC-OH (51 ± 246ng/mL) were found in 65 and 98% of cannabis-positive athletes' urine samples, respectively. In conclusion, in addition to THC-COOH, the pharmacologically active THC and THC-OH should be used as target analytes for doping urine analysis. In the case of light cannabis use, this may allow the estimation of more recent consumption, probably influencing performance during competitions. However, it is not possible to discriminate the intention of cannabis use, i.e., for recreational or doping purposes. Additionally, pharmacokinetic data of female volunteers are needed to interpret cannabis-positive doping cases of female athletes. Figure Urine concentration ranges of delta-9-tetrahydrocannabinol (THC) and its metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) in athletes tested cannabispositive (15ng/mL THC-COOH or more; N=81)