Department of Clinical Research, University of Berne, Murtenstr. 35, 3010 Berne, Switzerland.
Anal Bioanal Chem. 2010 Apr;396(7):2493-502. doi: 10.1007/s00216-009-3431-3. Epub 2010 Jan 30.
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-Delta(9)-tetrahydrocannabinol (THC-COOH), the cutoff being 15 ng/mL. However, the wide urinary detection window of the long-term metabolite of Delta(9)-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 70 mg THC per cigarette. Plasma and urine were collected up to 8 h and 11 days, respectively. Total THC, 11-hydroxy-Delta(9)-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 0.1-1.0 ng/mL. Eight puffs delivered a mean THC dose of 45 mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2-59.1, 0.1-3.9, and 0.4-16.4 ng/mL, respectively. Peak concentrations were observed at 5, 5-20, and 20-180 min. Urine levels were measured in the ranges 0.1-1.3, 0.1-14.4, and 0.5-38.2 ng/mL, peaking at 2, 2, and 6-24 h, respectively. The times of the last detectable levels were 2-8, 6-96, and 48-120 h. Besides high to very high THC-COOH levels (245 +/- 1,111 ng/mL), THC (3 +/- 8 ng/mL) and THC-OH (51 +/- 246 ng/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.
自 2004 年以来，大麻已被世界反兴奋剂机构禁止用于所有体育竞赛。此后的几年中，瑞士大约一半的阳性兴奋剂检测结果都与大麻消费有关。在兴奋剂尿检分析中，目标分析物是 11-去甲-9-羧基-Δ(9)-四氢大麻酚（THC-COOH），检测限为 15ng/mL。然而，Δ(9)-四氢大麻酚（THC）的长期代谢物在尿液中的检测窗口很宽，无法确定消费时间或对身体表现的影响。本研究的目的是评估具有较短尿液排泄时间的目标分析物。12 名男性志愿者吸食了一支标准化为每支 70mgTHC 的大麻香烟。分别在 8 小时和 11 天内采集血浆和尿液。水解后，通过固相萃取和气相色谱/质谱法测定总 THC、11-羟基-Δ(9)-四氢大麻酚（THC-OH）和 THC-COOH。定量限为 0.1-1.0ng/mL。8 口抽吸可提供平均 45mgTHC 剂量。总 THC、THC-OH 和 THC-COOH 的血浆水平分别在 0.2-59.1、0.1-3.9 和 0.4-16.4ng/mL 的范围内测量。在 5、5-20 和 20-180 分钟时观察到峰浓度。尿液水平在 0.1-1.3、0.1-14.4 和 0.5-38.2ng/mL 的范围内测量，分别在 2、2 和 6-24 小时时达到峰值。最后检测到的水平时间分别为 2-8、6-96 和 48-120 小时。除了高至非常高的 THC-COOH 水平（245±1111ng/mL）外，在 65%和 98%的大麻阳性运动员尿液样本中还发现了 THC（3±8ng/mL）和 THC-OH（51±246ng/mL）。总之，除了 THC-COOH 之外，还应将具有药理活性的 THC 和 THC-OH 用作兴奋剂尿液分析的目标分析物。在轻度吸食大麻的情况下，这可能允许估计最近的消费情况，可能会影响比赛期间的表现。然而，无法区分大麻使用的意图，即娱乐性或兴奋剂目的。此外，还需要女性志愿者的药代动力学数据来解释女性运动员的大麻阳性兴奋剂检测结果。
