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DOI: 10.1055/a-2249-7824
Development and Validation of a GC-FID Method for the Quantitation of Δ 8-Tetrahydrocannabinol and Impurities Found in Synthetic Δ 8-Tetrahydrocannabinol and Vaping Products
This study was supported by the United States Pharmacopeial Convention (USPC).Abstract
Concerns about health hazards associated with the consumption of trans-delta-8-tetrahydrocannabinol products were highlighted in public health advisories from the U. S. Food and Drug Administration and U. S. Centers for Disease Control and Prevention. Simple and rapid quantitative methods to determine trans-delta-8-tetrahydrocannabinol impurities are vital to analyze such products. In this study, a gas chromatography-flame ionization detection method was developed and validated for the determination of delta-8-tetrahydrocannabinol and some of its impurities (recently published) found in synthesized trans-delta-8-tetrahydrocannabinol raw material and included olivetol, cannabicitran, Δ 8-cis-iso-tetrahydrocannabinol, Δ 4-iso-tetrahydrocannabinol, iso-tetrahydrocannabifuran, cannabidiol, Δ 4,8-iso-tetrahydrocannabinol, Δ 8-iso-tetrahydrocannabinol, 4,8-epoxy-iso-tetrahydrocannabinol, trans-Δ 9-tetrahydrocannabinol, 8-hydroxy-iso-THC, 9α-hydroxyhexahydrocannabinol, and 9β-hydroxyhexahydrocannabinol. Validation of the method was assessed according to the International Council for Harmonization guidelines and confirmed linearity with R2 ≥ 0.99 for all the target analytes. The limit of detection and limit of quantitation were 1.5 and 5 µg/mL, respectively, except for olivetol, which had a limit of detection of 3 µg/mL and a limit of quantitation of 10 µg/mL. Method precision was calculated as % relative standard deviation and the values were less than 8.4 and 9.9% for the intraday precision and inter-day precision, respectively. The accuracy ranged from 85 to 118%. The method was then applied to the analysis of 21 commercially marketed vaping products claiming to contain delta-8-tetrahydrocannabinol. The products analyzed by this method have various levels of these impurities, with all products far exceeding the 0.3% of trans-Δ 9-tetrahydrocannabinol limit for hemp under the Agriculture Improvement Act of 2018. The developed gas chromatography-flame ionization detection method can be an important tool for monitoring delta-8-tetrahydrocannabinol impurities in commercial products.
Publication History
Received: 14 September 2023
Accepted after revision: 14 January 2024
Article published online:
22 February 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
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References
- 1 Radwan MM, Wanas AS, Chandra S, ElSohly MA. Natural Cannabinoids of Cannabis and Methods of Analysis. In: Chandra S, Lata H, ElSohly M. editors Cannabis sativa L. – Botany and Biotechnology. Cham: Springer; 2017: 161-182
- 2 Rock EM, Parker LA. Constituents of Cannabis Sativa . In: Murillo-Rodriguez E, Pandi-Perumal SR, Monti JM. editors Cannabinoids and Neuropsychiatric Disorders. Cham: Springer International Publishing; 2021: 1-13
- 3 Moore E. An Overview of the Phytochemistry of Cannabis sativa L. IDOSR-JBBAF 2020; 5: 39-44
- 4 ElSohly MA, Slade D. Chemical constituents of marijuana: The complex mixture of natural cannabinoids. Life Sci 2005; 78: 539-548
- 5 Degenhardt F, Stehle F, Kayser O. The Biosynthesis of Cannabinoids. In: Preedy VR. editor Handbook of Cannabis and Related Pathologies. San Diego: Academic Press; 2017: 13-23
- 6 Barčauskaitė K, Bakšinskaitė A, Szumny A, Tilvikienė V. Variation of secondary metabolites in Cannabis sativa L. inflorescences under applied agrotechnological measures. Ind Crops Prod 2022; 188: 115570
- 7 Sarma ND, Waye A, ElSohly MA, Brown PN, Elzinga S, Johnson HE, Marles RJ, Melanson JE, Russo E, Deyton L, Hudalla C, Vrdoljak GA, Wurzer JH, Khan IA, Kim NC, Giancaspro GI. Cannabis Inflorescence for Medical Purposes: USP Considerations for Quality Attributes. J Nat Prod 2020; 83 (04) 1334-1351
- 8 Congressional Budget Office. H.R.2–115th Congress (2017–2018): Agriculture Improvement Act of 2018. Accessed April 19, 2023 at: https://www.congress.gov/bill/115th-congress/house-bill/2/text
- 9 Cerino P, Buonerba C, Cannazza G, DʼAuria J, Ottoni E, Fulgione A, Di Stasio A, Pierri B, Gallo A. A review of hemp as food and nutritional supplement. Cannabis Cannabinoid Res 2021; 6: 19-27
- 10 Hollister LE, Gillespie H. Delta‐8‐ and delta‐9‐tetrahydrocannabinol comparison in man by oral and intravenous administration. Clin Pharmacol Ther 1973; 14: 353-357
- 11 Sallan SE, Zinberg NE, Frei 3rd E. Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med 1975; 293: 795-797
- 12 Syed YY, McKeage K, Scott LJ. Delta-9-tetrahydrocannabinol/cannabidiol (Sativex®): A review of its use in patients with moderate to severe spasticity due to multiple sclerosis. Drugs 2014; 74: 563-578
- 13 Flach AJ. Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma. Trans Am Ophthalmol Soc 2002; 100: 215-224
- 14 Livingston MD, Walker A, Cannell MB, Rossheim ME. Popularity of delta-8 THC on the Internet across US States, 2021. Am J Public Health 2022; 112: 296-299
- 15 Leas EC, Nobles AL, Shi Y, Hendrickson E. Public interest in Δ8-Tetrahydrocannabinol (delta-8-THC) increased in US states that restricted Δ9-Tetrahydrocannabinol (delta-9-THC) use. Int J Drug Policy 2022; 101: 103557
- 16 Johnson-Arbor K, Smolinske S. The current state of delta-8 THC. Am J Emerg Med 2022; 56: 259-261
- 17 Zulfiqar S. Best Delta 8 Products for Depression Reviewed (2023). Accessed August 5, 2023 at: https://cbdthinker.com/best-delta-8-thc-for-depression/
- 18 U.S. Department of Health and Human Services FDA. Center for Drug Evaluation and Research (CDER). Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research Guidance for Industry. Accessed April 19, 2023 at: https://www.fda.gov/media/164690/download
- 19 United States Pharmacopeia Cannabis Panel. USP Cannabis Panel statement on delta 8-THC. Accessed April 19, 2023 at: https://www.usp.org/sites/default/files/usp/document/our-science/usp-delta-8-final-12-2-21.pdf
- 20 Gaoni Y, Mechoulam R. Hashish–VII: The isomerization of cannabidiol to tetrahydrocannabinols. Tetrahedron 1966; 22: 1481-1488
- 21 Golombek P, Müller M, Barthlott I, Sproll C, Lachenmeier DW. Conversion of cannabidiol (CBD) into psychotropic cannabinoids including tetrahydrocannabinol (THC): a controversy in the scientific literature. Toxics 2020; 8: 41
- 22 Nalli Y, Jan S, Lauro G, Ur Rasool J, Lone WI, Sarkar AR, Banday J, Bifulco G, Laatsch H, Syed SH. Isolation, synthesis and structure determination of cannabidiol derivatives and their cytotoxic activities. Nat Prod Res 2021; 35: 471-480
- 23 Webster GB, Sarna LP, Mechoulam R. Conversion of CBD to Δ 8-THC and Δ 9-THC. US Patent 7399872, 2008
- 24 Meehan-Atrash J, Rahman I. Novel Δ 8-tetrahydrocannabinol vaporizers contain unlabeled adulterants, unintended byproducts of chemical synthesis, and heavy metals. Chem Res Toxicol 2021; 35: 73-76
- 25 Geci M, Scialdone M, Tishler J. The dark side of cannabidiol: The unanticipated social and clinical implications of synthetic Δ 8-THC. Cannabis Cannabinoid Res 2022; 8: 270-282
- 26 Ray CL, Bylo MP, Pescaglia J, Gawenis JA, Greenlief CM. Delta-8 tetrahydrocannabinol product impurities. Molecules 2022; 27: 6924
- 27 U.S. Food and Drug Administration. FDA Issues Warning Letters to Companies Illegally Selling CBD and Delta-8 THC Product. Accessed April 19, 2023 at: https://www.fda.gov/news-events/press-announcements/fda-issues-warning-letters-companies-illegally-selling-cbd-and-delta-8-thc-products
- 28 U.S. food and Drug Administration. 5 Things to Know about Delta-8-Tetrahydrocannabinol-Delta-8-THC. Accessed April 19, 2023 at: https://www.fda.gov/consumers/consumer-updates/5-things-know-about-delta-8-tetrahydrocannabinol-delta-8-thc
- 29 Colorado Department of Public Health and Environment. Production and/or Use of Chemically Modified or Converted Industrial Hemp Cannabinoids. Accessed April 19, 2023 at: https://www.denvergov.org/files/assets/public/public-health-and-environment/documents/phi/dehs_mfdfd_industrialhemp_delta8_notice_cdphe_logo_051421.pdf
- 30 Radwan MM, Wanas AS, Gul W, Ibrahim EA, ElSohly MA. Isolation and characterization of impurities in commercially marketed Δ 8-THC products. J Nat Prod 2023; 86: 822-829
- 31 ICH Harmonised Tripartite Guideline. Validation of analytical procedures: text and methodology. Q2 (R1). 2005. Accessed April 19, 2023 at: https://somatek.com/wp-content/uploads/2014/06/sk140605h.pdf
- 32 U.S. Department of Health and Human Services FDA, Center for Drug Evaluation and Research (CDER). Botanical Drug Development Guidance for Industry. Accessed April 19, 2023 at: https://www.fda.gov/media/93113/download