Scheidweiler Karl B, Newmeyer Matthew N, Barnes Allan J, Huestis Marilyn A
Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
Chemistry and Drug Metabolism Section, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA; Program in Toxicology, University of Maryland, Baltimore, MD, USA.
J Chromatogr A. 2016 Jul 1;1453:34-42. doi: 10.1016/j.chroma.2016.05.024. Epub 2016 May 7.
Identifying recent cannabis intake is confounded by prolonged cannabinoid excretion in chronic frequent cannabis users. We previously observed detection times ≤2.1h for cannabidiol (CBD) and cannabinol (CBN) and Δ(9)-tetrahydrocannabinol (THC)-glucuronide in whole blood after smoking, suggesting their applicability for identifying recent intake. However, whole blood collection may not occur for up to 4h during driving under the influence of drugs investigations, making a recent-use marker with a 6-8h detection window helpful for improving whole blood cannabinoid interpretation. Other minor cannabinoids cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV), and its metabolite 11-nor-9-carboxy-THCV (THCVCOOH) might also be useful. We developed and validated a sensitive and specific liquid chromatography-tandem mass spectrometry method for quantification of THC, its phase I and glucuronide phase II metabolites, and 5 five minor cannabinoids. Cannabinoids were extracted from 200μL whole blood via disposable pipette extraction, separated on a C18 column, and detected via electrospray ionization in negative mode with scheduled multiple reaction mass spectrometric monitoring. Linear ranges were 0.5-100μg/L for THC and 11-nor-9-carboxy-THC (THCCOOH); 0.5-50μg/L for 11-hydroxy-THC (11-OH-THC), CBD, CBN, and THC-glucuronide; 1-50μg/L for CBG, THCV, and THCVCOOH; and 5-500μg/L for THCCOOH-glucuronide. Inter-day accuracy and precision at low, mid and high quality control (QC) concentrations were 95.1-113% and 2.4-8.5%, respectively (n=25). Extraction recoveries and matrix effects at low and high QC concentrations were 54.0-84.4% and -25.8-30.6%, respectively. By simultaneously monitoring multiple cannabinoids and metabolites, identification of recent cannabis administration or discrimination between licit medicinal and illicit recreational cannabis use can be improved.
在慢性频繁使用大麻的人群中，由于大麻素排泄时间延长，确定近期是否使用过大麻变得复杂。我们之前观察到，吸烟后全血中大麻二酚（CBD）、大麻酚（CBN）和Δ⁹-四氢大麻酚（THC）-葡萄糖醛酸的检测时间≤2.1小时，这表明它们适用于确定近期是否使用过大麻。然而，在药物影响下驾驶的调查过程中，长达4小时内可能无法采集全血，因此具有6 - 8小时检测窗口的近期使用标志物有助于改进全血大麻素的解读。其他微量大麻素，如大麻萜酚（CBG）、Δ⁹-四氢大麻酚酸（THCV）及其代谢物11-去甲-9-羧基-THCV（THCVCOOH）可能也有用。我们开发并验证了一种灵敏且特异的液相色谱-串联质谱法，用于定量THC、其I相和葡萄糖醛酸化II相代谢物以及5种微量大麻素。通过一次性移液器萃取从200μL全血中提取大麻素，在C18柱上进行分离，并通过电喷雾电离在负离子模式下进行预定多反应质谱监测。THC和11-去甲-9-羧基-THC（THCCOOH）的线性范围为0.5 - 100μg/L；11-羟基-THC（11-OH-THC）、CBD、CBN和THC-葡萄糖醛酸的线性范围为0.5 - 50μg/L；CBG、THCV和THCVCOOH的线性范围为1 - 50μg/L；THCCOOH-葡萄糖醛酸的线性范围为5 - 500μg/L。低、中、高浓度质量控制（QC）下的日间准确度和精密度分别为95.1 - 113%和2.4 - 8.5%（n = 25）。低、高浓度QC下的萃取回收率和基质效应分别为54.0 - 84.4%和 - 25.8 - 30.6%。通过同时监测多种大麻素及其代谢物，可以改进近期大麻使用情况的鉴定，或区分合法药用大麻和非法娱乐用大麻。
