癫痫患者在接受对照给药后，通过体积吸收微取样和液相色谱-串联质谱法测定人血液中的大麻二酚、Δ-四氢大麻酚及其代谢物。
Cannabidiol, ∆-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS/MS following controlled administration in epilepsy patients.
作者信息
Pigliasco Federica, Malaca Sara, Lo Faro Alfredo Fabrizio, Tini Anastasio, Cangemi Giuliana, Cafaro Alessia, Barco Sebastiano, Riva Antonella, Pisati Angelica, Amadori Elisabetta, Striano Pasquale, Tagliabracci Adriano, Huestis Marilyn Ann, Busardò Francesco Paolo
机构信息
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
Department of Excellence-Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, Italy.
出版信息
Front Pharmacol. 2022 Oct 24;13:1038754. doi: 10.3389/fphar.2022.1038754. eCollection 2022.
Cannabidiol (CBD) exhibits anti-inflammatory, anxiolytic, antiseizure, and neuroprotective proprieties without addictive or psychotropic side effects, as opposed to Δ-tetrahydrocannabinol (THC). While recreational cannabis contains higher THC and lower CBD concentrations, medical cannabis contains THC and CBD in different ratios, along with minor phytocannabinoids, terpenes, flavonoids and other chemicals. A volumetric absorptive microsampling (VAMS) method combined with ultra-high-performance liquid chromatography coupled with mass spectrometry in tandem for quantification of CBD, THC and their respective metabolites: cannabidiol-7-oic acid (7-COOH-CBD); 7-hydroxy-cannabidiol (7-OH-CBD); 6-alpha-hydroxy-cannabidiol (6-α-OH-CBD); and 6-beta-hydroxycannabidiol (6-β-OH-CBD); 11- Hydroxy-Δ-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-Δ-tetrahydrocannabinol (THCCOOH). After overnight enzymatic glucuronide hydrolysis at 37°C, samples underwent acidic along with basic liquid-liquid extraction with hexane: ethyl acetate (9:1, v/v). Chromatographic separation was carried out on a C18 column, with the mass spectrometer operated in multiple reaction monitoring mode and negative electrospray ionization. Seven patients with intractable epilepsy were dosed with various CBD-containing formulations and blood collected just before their daily morning administration. The method was validated following international guidelines in toxicology. Linear ranges were (ng/ml) 0.5-25 THC, 11-OH-THC, THCCOOH, 6-α-OH-CBD and 6-β-OH-CBD; 10-500 CBD and 7-OH-CBD; and 20-5000 7-COOH-CBD. 7-COOH-CBD was present in the highest concentrations, followed by 7-OH-CBD and CBD. This analytical method is useful for investigating CBD, THC and their major metabolites in epilepsy patients treated with CBD preparations employing a minimally invasive microsampling technique requiring only 30 µL blood.
与Δ-四氢大麻酚（THC）不同，大麻二酚（CBD）具有抗炎、抗焦虑、抗癫痫和神经保护特性，且无成瘾性或精神副作用。娱乐用大麻中THC含量较高而CBD浓度较低，医用大麻则含有不同比例的THC和CBD，以及少量植物大麻素、萜类化合物、黄酮类化合物和其他化学物质。采用体积吸收微采样（VAMS）方法，结合超高效液相色谱-串联质谱法，用于定量分析CBD、THC及其各自的代谢产物：大麻二酚-7-酸（7-COOH-CBD）；7-羟基大麻二酚（7-OH-CBD）；6-α-羟基大麻二酚（6-α-OH-CBD）；6-β-羟基大麻二酚（6-β-OH-CBD）；11-羟基-Δ-四氢大麻酚（11-OH-THC）和11-去甲-9-羧基-Δ-四氢大麻酚（THCCOOH）。在37°C下进行过夜酶促葡糖醛酸苷水解后，样品用己烷：乙酸乙酯（9:1，v/v）进行酸性和碱性液-液萃取。在C18柱上进行色谱分离，质谱仪采用多反应监测模式和负电喷雾电离。7例难治性癫痫患者服用各种含CBD制剂，并在每日早晨给药前采集血液。该方法按照国际毒理学指南进行了验证。线性范围为（ng/ml）：0.5-25的THC、11-OH-THC、THCCOOH、6-α-OH-CBD和6-β-OH-CBD；10-500的CBD和7-OH-CBD；以及20-5000的7-COOH-CBD。7-COOH-CBD浓度最高，其次是7-OH-CBD和CBD。这种分析方法对于使用仅需30μL血液的微创微采样技术，研究接受CBD制剂治疗的癫痫患者体内的CBD、THC及其主要代谢产物很有用。
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