Incomplete Decarboxylation of Acidic Cannabinoids in GC-MS Leads to Underestimation of the Total Cannabinoid Content in Cannabis Oils Without Derivatization.

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Martina Franzin, Rebecca Di Lenardo, Rachele Ruoso, Riccardo Addobbati
{"title":"Incomplete Decarboxylation of Acidic Cannabinoids in GC-MS Leads to Underestimation of the Total Cannabinoid Content in Cannabis Oils Without Derivatization.","authors":"Martina Franzin, Rebecca Di Lenardo, Rachele Ruoso, Riccardo Addobbati","doi":"10.3390/pharmaceutics17030334","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background</b>: Cannabis oil titration consists of quantification of the acidic precursors tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) and their decarboxylated products, the active neutral cannabinoids delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and is recommended to ensure galenic preparation quality through gas and liquid chromatography coupled with mass spectrometry (GC-MS; LC-MS). Analyses by LC-MS and GC-MS involving derivatization allow for detection of acidic and neutral cannabinoids; on the contrary, GC-MS without derivatization determines only neutral cannabinoids due to high temperature-decarboxylation occurring in the injection system. However, it is not clear if decarboxylation is complete. <b>Methods</b>: Different GC-MS methods with (BSTFA: TMCS and pyridine; incubation at 60 °C for 25 min) or without derivatization and an LC-MS method were developed for cannabinoid quantification. The total Δ9-THC and CBD yield of recovery were compared between the methods by testing laboratory samples with known concentrations of THCA and CBDA (total Δ9-THC and CBD: 175-351-702 ng/mL) and real cannabis oil samples (n = 6). <b>Results</b>: The total Δ9-THC and CBD yield of recovery were determined using LC-MS and GC-MS with derivatization, but not using GC-MS without derivatization (decarboxylation conversion rate of about 50-60%). No high deviation (<10%) in the total neutral cannabinoid concentrations in real cannabis oil samples was noticed, probably due to the low content of acidic forms in the original galenic preparation. <b>Conclusions</b>: This study raised awareness about the potential underestimation of the total Δ9-THC and CBD content in cannabis oils when quantification is performed by GC-MS without derivatization. The advice for pharmacists is to perform complete decarboxylation to convert all acidic precursors in neutral cannabinoids.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944363/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/pharmaceutics17030334","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Cannabis oil titration consists of quantification of the acidic precursors tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) and their decarboxylated products, the active neutral cannabinoids delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and is recommended to ensure galenic preparation quality through gas and liquid chromatography coupled with mass spectrometry (GC-MS; LC-MS). Analyses by LC-MS and GC-MS involving derivatization allow for detection of acidic and neutral cannabinoids; on the contrary, GC-MS without derivatization determines only neutral cannabinoids due to high temperature-decarboxylation occurring in the injection system. However, it is not clear if decarboxylation is complete. Methods: Different GC-MS methods with (BSTFA: TMCS and pyridine; incubation at 60 °C for 25 min) or without derivatization and an LC-MS method were developed for cannabinoid quantification. The total Δ9-THC and CBD yield of recovery were compared between the methods by testing laboratory samples with known concentrations of THCA and CBDA (total Δ9-THC and CBD: 175-351-702 ng/mL) and real cannabis oil samples (n = 6). Results: The total Δ9-THC and CBD yield of recovery were determined using LC-MS and GC-MS with derivatization, but not using GC-MS without derivatization (decarboxylation conversion rate of about 50-60%). No high deviation (<10%) in the total neutral cannabinoid concentrations in real cannabis oil samples was noticed, probably due to the low content of acidic forms in the original galenic preparation. Conclusions: This study raised awareness about the potential underestimation of the total Δ9-THC and CBD content in cannabis oils when quantification is performed by GC-MS without derivatization. The advice for pharmacists is to perform complete decarboxylation to convert all acidic precursors in neutral cannabinoids.

GC-MS中酸性大麻素的不完全脱羧导致未衍生的大麻油中总大麻素含量的低估。
背景:大麻油滴定包括对酸性前体四氢大麻酚酸(THCA)和大麻二酸(CBDA)及其脱羧产物、活性中性大麻素δ -9-四氢大麻酚(Δ9-THC)和大麻二酚(CBD)的定量,建议通过气相色谱-液相色谱-质谱联用(GC-MS)来确保大麻油制剂的质量;质)。包括衍生化的LC-MS和GC-MS分析允许检测酸性和中性大麻素;相反,没有衍生化的GC-MS只能测定由于注射系统中高温脱羧而产生的中性大麻素。然而,脱羧是否完全尚不清楚。方法:采用(BSTFA: TMCS和吡啶)不同的GC-MS方法;在60°C孵育25分钟)或不衍生化和LC-MS方法建立大麻素的定量。通过检测已知THCA和CBDA浓度的实验室样品(总Δ9-THC和CBD: 175-351-702 ng/mL)和真实大麻油样品(n = 6),比较两种方法回收的总Δ9-THC和CBD得率。结果:采用带衍生化的LC-MS和GC-MS测定回收的总Δ9-THC和CBD得率,不采用不带衍生化的GC-MS测定(脱羧转化率约为50-60%)。结论:本研究提高了人们对不进行衍生化的GC-MS定量时可能低估大麻油中总Δ9-THC和CBD含量的认识。药剂师的建议是执行完全脱羧转化中性大麻素的所有酸性前体。
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
Pharmaceutics
Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍: Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications,  and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
×
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:481959085
Book学术官方微信