Identification of Tetrahydrocannabidiol Metabolites in Human Urine.

IF 2.7 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS
Willi Schirmer, Isabelle Mösch, Stefan Schürch, Wolfgang Weinmann
{"title":"Identification of Tetrahydrocannabidiol Metabolites in Human Urine.","authors":"Willi Schirmer, Isabelle Mösch, Stefan Schürch, Wolfgang Weinmann","doi":"10.1002/dta.3945","DOIUrl":null,"url":null,"abstract":"<p><p>Tetrahydrocannabidiol (H4CBD) is an emerging semisynthetic cannabinoid, which has been known since 1940. Like hexahydrocannabinol (HHC), it is easily obtained by hydrogenation of available phytocannabinoids, in the case of H4CBD by hydrogenation of cannabidiol (CBD). H4CBD shows a weak affinity for the CB<sub>1</sub> receptor, but it is unclear if H4CBD shows psychoactive properties, as reports from users are divided. Only a few countries have placed H4CBD under their narcotic substance law, for example, France and Switzerland. The aim of this study was to identify human Phase I and II metabolites in urine as potential forensic targets. The H4CBD used for this study was bought from an online store and analyzed beforehand using GC-MS. The Phase I and II metabolites were identified using LC-HR-MS/MS and GC-MS after trimethylsilylation. The found H4CBD metabolites were carboxylated, hydroxylated, and bishydroxylated species and their glucuronides with hydroxylation and carboxylation positions on the alicyclic moiety and on the side chain. The tentatively identified metabolites were the carboxylic acids 5″-COOH-H4CBD and 7-COOH-H4CBD, the hydroxylated metabolites (1R,6R)-OH-H4CBD, (1R,6S)-OH-H4CBD, two epimers of 2″-OH-H4CBD, and both epimers of 7-OH-H4CBD. The identified bishydroxylated metabolites were side-chain hydroxylated derivatives of 7-OH-H4CBD. Various other hydroxylated metabolites were found, but their exact hydroxylation positions could not be determined. Some ESI+ spectra of the metabolites showed very unusual fragmentation patterns, like the loss of both oxygens from the resorcinol moiety with subsequent ring contraction and the appearance of radical cations for Phase II metabolites. These unusual patterns were noticed for H4CBD and its side-chain-altered metabolites.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Testing and Analysis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/dta.3945","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0

Abstract

Tetrahydrocannabidiol (H4CBD) is an emerging semisynthetic cannabinoid, which has been known since 1940. Like hexahydrocannabinol (HHC), it is easily obtained by hydrogenation of available phytocannabinoids, in the case of H4CBD by hydrogenation of cannabidiol (CBD). H4CBD shows a weak affinity for the CB1 receptor, but it is unclear if H4CBD shows psychoactive properties, as reports from users are divided. Only a few countries have placed H4CBD under their narcotic substance law, for example, France and Switzerland. The aim of this study was to identify human Phase I and II metabolites in urine as potential forensic targets. The H4CBD used for this study was bought from an online store and analyzed beforehand using GC-MS. The Phase I and II metabolites were identified using LC-HR-MS/MS and GC-MS after trimethylsilylation. The found H4CBD metabolites were carboxylated, hydroxylated, and bishydroxylated species and their glucuronides with hydroxylation and carboxylation positions on the alicyclic moiety and on the side chain. The tentatively identified metabolites were the carboxylic acids 5″-COOH-H4CBD and 7-COOH-H4CBD, the hydroxylated metabolites (1R,6R)-OH-H4CBD, (1R,6S)-OH-H4CBD, two epimers of 2″-OH-H4CBD, and both epimers of 7-OH-H4CBD. The identified bishydroxylated metabolites were side-chain hydroxylated derivatives of 7-OH-H4CBD. Various other hydroxylated metabolites were found, but their exact hydroxylation positions could not be determined. Some ESI+ spectra of the metabolites showed very unusual fragmentation patterns, like the loss of both oxygens from the resorcinol moiety with subsequent ring contraction and the appearance of radical cations for Phase II metabolites. These unusual patterns were noticed for H4CBD and its side-chain-altered metabolites.

人尿中四氢大麻二酚代谢物的鉴定。
四氢大麻二酚(H4CBD)是一种新兴的半合成大麻素,自1940年以来一直为人所知。与六氢大麻酚(HHC)一样,它很容易通过可用的植物大麻素加氢获得,在H4CBD的情况下,通过大麻二酚(CBD)的加氢获得。H4CBD显示出对CB1受体的弱亲和力,但目前尚不清楚H4CBD是否具有精神活性,因为来自使用者的报告存在分歧。只有法国和瑞士等少数国家将H4CBD纳入其麻醉药品法。本研究的目的是鉴定人类尿液中的I期和II期代谢物作为潜在的法医靶点。本研究中使用的H4CBD是从网上商店购买的,事先使用气相色谱-质谱分析。三甲基硅化后的I期和II期代谢物采用LC-HR-MS/MS和GC-MS进行鉴定。发现的H4CBD代谢物有羧基化、羟基化和双羟基化的种类及其葡萄糖醛酸盐,羟基化和羧基化位置在脂环部分和侧链上。初步鉴定的代谢物为羧酸5″-COOH-H4CBD和7-COOH-H4CBD,羟基化代谢物(1R,6R)-OH-H4CBD, (1R,6S)-OH-H4CBD, 2″-OH-H4CBD的两个外显体和7-OH-H4CBD的两个外显体。鉴定的双羟基化代谢物是7-OH-H4CBD的侧链羟基化衍生物。发现了各种其他羟基化代谢物,但它们的确切羟基化位置无法确定。代谢物的一些ESI+光谱显示出非常不寻常的断裂模式,如间苯二酚部分的两个氧的损失,随后的环收缩和II期代谢物的自由基阳离子的出现。这些不寻常的模式在H4CBD及其侧链改变的代谢物中被注意到。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Drug Testing and Analysis
Drug Testing and Analysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL
CiteScore
5.90
自引率
24.10%
发文量
191
审稿时长
2.3 months
期刊介绍: As the incidence of drugs escalates in 21st century living, their detection and analysis have become increasingly important. Sport, the workplace, crime investigation, homeland security, the pharmaceutical industry and the environment are just some of the high profile arenas in which analytical testing has provided an important investigative tool for uncovering the presence of extraneous substances. In addition to the usual publishing fare of primary research articles, case reports and letters, Drug Testing and Analysis offers a unique combination of; ‘How to’ material such as ‘Tutorials’ and ‘Reviews’, Speculative pieces (‘Commentaries’ and ‘Perspectives'', providing a broader scientific and social context to the aspects of analytical testing), ‘Annual banned substance reviews’ (delivering a critical evaluation of the methods used in the characterization of established and newly outlawed compounds). Rather than focus on the application of a single technique, Drug Testing and Analysis employs a unique multidisciplinary approach to the field of controversial compound determination. Papers discussing chromatography, mass spectrometry, immunological approaches, 1D/2D gel electrophoresis, to name just a few select methods, are welcomed where their application is related to any of the six key topics listed below.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信