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慢性大麻使用者尿液中Δ9-四氢大麻酚排泄时间延长,使其无法用作新药暴露的生物标志物。

Extended urinary Delta9-tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure.

作者信息

Lowe Ross H, Abraham Tsadik T, Darwin William D, Herning Ronald, Cadet Jean Lud, Huestis Marilyn A

机构信息

Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Biomedical Research Center, 251 Bayview Boulevard, Suite 05A721, Baltimore, MD 21224, USA.

出版信息

Drug Alcohol Depend. 2009 Nov 1;105(1-2):24-32. doi: 10.1016/j.drugalcdep.2009.05.027. Epub 2009 Jul 23.

Abstract

BACKGROUND

Generally, urinary 11-nor-9-carboxy-Delta9-tetrahydrocannabinol (THCCOOH) after alkaline hydrolysis is monitored to detect cannabis exposure, although last use may have been weeks prior in chronic cannabis users. Delta9-Tetrahydrocannabinol (THC) and 11-hydroxy-THC (11-OH-THC) concentrations in urine following Escherichia coli beta-glucuronidase hydrolysis were proposed as biomarkers of recent (within 8h) cannabis use.

OBJECTIVE

To test the validity of THC and 11-OH-THC in urine as indicators of recent cannabis use.

METHODS

Monitor urinary cannabinoid excretion in 33 chronic cannabis smokers who resided on a secure research unit under 24h continuous medical surveillance. All urine specimens were collected individually ad libidum for up to 30 days, were hydrolyzed with a tandem E. coli beta-glucuronidase/base procedure, and analyzed for THC, 11-OH-THC and THCCOOH by one- and two-dimensional-cryotrap gas chromatography mass spectrometry (2D-GCMS) with limits of quantification of 2.5 ng/mL.

RESULTS

Extended excretion of THC and 11-OH-THC in chronic cannabis users' urine was observed during monitored abstinence; 14 of 33 participants had measurable THC in specimens collected at least 24h after abstinence initiation. Seven subjects had measurable THC in urine for 3, 3, 4, 7, 7, 12, and 24 days after cannabis cessation. 11-OH-THC and THCCOOH were detectable in urine specimens from one heavy, chronic cannabis user for at least 24 days.

CONCLUSION

For the first time, extended urinary excretion of THC and 11-OH-THC is documented for at least 24 days, negating their effectiveness as biomarkers of recent cannabis exposure, and substantiating long terminal elimination times for urinary cannabinoids following chronic cannabis smoking.

摘要

背景

一般来说,尽管慢性大麻使用者上次使用大麻可能是几周前,但通过监测碱性水解后的尿液中11-去甲-9-羧基-Δ⁹-四氢大麻酚(THCCOOH)来检测大麻暴露情况。有人提出,经大肠杆菌β-葡萄糖醛酸酶水解后的尿液中Δ⁹-四氢大麻酚(THC)和11-羟基-THC(11-OH-THC)浓度可作为近期(8小时内)大麻使用的生物标志物。

目的

检验尿液中THC和11-OH-THC作为近期大麻使用指标的有效性。

方法

对33名居住在安全研究单位且接受24小时连续医学监测的慢性大麻吸烟者的尿大麻素排泄情况进行监测。所有尿液标本均按需单独收集,最长收集30天,采用串联大肠杆菌β-葡萄糖醛酸酶/碱法进行水解,并通过一维和二维低温捕集气相色谱-质谱联用仪(2D-GCMS)分析THC、11-OH-THC和THCCOOH,定量限为2.5 ng/mL。

结果

在监测的禁欲期内,观察到慢性大麻使用者尿液中THC和11-OH-THC排泄时间延长;33名参与者中有14人在禁欲开始至少24小时后采集的标本中检测到可测量的THC。7名受试者在停止使用大麻后的3、3、4、7、7、12和24天尿液中检测到可测量的THC。在一名重度慢性大麻使用者的尿液标本中,至少24天可检测到11-OH-THC和THCCOOH。

结论

首次记录到THC和11-OH-THC在尿液中的排泄时间至少延长24天,这否定了它们作为近期大麻暴露生物标志物的有效性,并证实了慢性吸食大麻后尿大麻素的长终末消除时间。

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