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