Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21124, USA.
Currently at The Lambert Center for the Study of Medicinal Cannabis and Hemp, Institute on Emerging Health Professions, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Drug Test Anal. 2019 Jul;11(7):968-975. doi: 10.1002/dta.2576. Epub 2019 Mar 15.
Variability in urine dilution complicates urine cannabinoid test interpretation. Normalizing urine cannabinoid concentrations to specific gravity (SG) or creatinine was proposed to account for donors' hydration states. In this study, all urine voids were individually collected from eight frequent and eight occasional cannabis users for up to 85 hours after each received on separate occasions 50.6 mg Δ9-tetrahydrocannabinol (THC) by smoking, vaporization, and oral ingestion in a randomized, within-subject, double-blind, double-dummy, placebo-controlled protocol. Each urine void was analyzed for 11 cannabinoids and phase I and II metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS), SG, and creatinine. Normalized urine concentrations were log transformed to create normal distributions, and Pearson correlation coefficients determined the degree of association between the two normalization methods. Repeated-measures linear regression determined if the degree of association differed by frequent or occasional cannabis use, or route of administration after adjusting for gender and time since dosing. Of 1880 urine samples examined, only 11-nor-9-carboxy-THC (THCCOOH), THCCOOH-glucuronide, THC-glucuronide, and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCVCOOH) were greater than the method's limits of quantification (LOQs). Associations between SG- and creatinine-normalized concentrations exceeded 0.90. Repeated-measures regression analysis found small but statistically significant differences in the degree of association between normalization methods for THCCOOH and THCCOOH-glucuronide in frequent vs occasional smokers, and in THCVCOOH and THC-glucuronide by route of administration. For the first time, SG- and creatinine-normalized urine cannabinoid concentrations were evaluated in frequent and occasional cannabis users and following oral, smoked, and inhaled cannabis. Both normalization methods reduced variability, improving the interpretation of urine cannabinoid concentrations and methods were strongly correlated.
尿液稀释的变异性使尿液中大麻素测试的解释变得复杂。为了说明供体的水合状态，有人提出将尿液中大麻素浓度标准化为比重（SG）或肌酐。在这项研究中，每个尿液样本都是从 8 名经常和 8 名偶尔吸食大麻的人单独收集的，他们分别在不同场合下通过吸烟、蒸发和口服摄入 50.6 毫克 Δ9-四氢大麻酚（THC），采用随机、在个体内、双盲、双模拟、安慰剂对照的方案。通过液相色谱-串联质谱法（LC-MS/MS）、SG 和肌酐对每个尿液样本进行了 11 种大麻素和 I 期和 II 期代谢物的分析。对标准化后的尿液浓度进行对数转换，以创建正态分布，然后使用 Pearson 相关系数确定两种标准化方法之间的关联程度。使用重复测量线性回归确定在调整性别和给药后时间后，关联程度是否因经常或偶尔使用大麻以及给药途径而异。在检查的 1880 个尿液样本中，只有 11-去甲-9-羧基-THC（THCCOOH）、THCCOOH-葡萄糖醛酸、THC-葡萄糖醛酸和 11-去甲-9-羧基-Δ9-四氢大麻酚（THCVCOOH）大于方法的定量下限（LOQ）。SG-和肌酐标准化浓度之间的相关性超过 0.90。重复测量回归分析发现，在经常和偶尔吸烟者中，THCCOOH 和 THCCOOH-葡萄糖醛酸以及不同给药途径中，THCVCOOH 和 THC-葡萄糖醛酸的两种标准化方法之间的关联程度存在微小但具有统计学意义的差异。这是首次在经常和偶尔使用大麻的人群中以及口服、吸烟和吸入大麻后，对 SG-和肌酐标准化尿液大麻素浓度进行评估。两种标准化方法均降低了变异性，改善了尿液中大麻素浓度的解释，方法之间具有很强的相关性。
