Cannabidiol, ∆9-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS/MS following controlled administration in epilepsy patients
Cannabidiol (CBD) exhibits anti-inflammatory, anxiolytic, antiseizure, and neuroprotective proprieties without addictive or psychotropic side effects, as opposed to Δ9-tetrahydrocannabinol (THC). While recreational cannabis contains higher THC and lower CBD concentrations, medical cannabis contains...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1038754/full |
| _version_ | 1798030806907617280 |
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| author | Federica Pigliasco Sara Malaca Alfredo Fabrizio Lo Faro Anastasio Tini Giuliana Cangemi Alessia Cafaro Alessia Cafaro Sebastiano Barco Antonella Riva Angelica Pisati Elisabetta Amadori Pasquale Striano Pasquale Striano Adriano Tagliabracci Marilyn Ann Huestis Francesco Paolo Busardò |
| author_facet | Federica Pigliasco Sara Malaca Alfredo Fabrizio Lo Faro Anastasio Tini Giuliana Cangemi Alessia Cafaro Alessia Cafaro Sebastiano Barco Antonella Riva Angelica Pisati Elisabetta Amadori Pasquale Striano Pasquale Striano Adriano Tagliabracci Marilyn Ann Huestis Francesco Paolo Busardò |
| author_sort | Federica Pigliasco |
| collection | DOAJ |
| description | Cannabidiol (CBD) exhibits anti-inflammatory, anxiolytic, antiseizure, and neuroprotective proprieties without addictive or psychotropic side effects, as opposed to Δ9-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-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-Δ9-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. |
| first_indexed | 2024-04-11T19:47:19Z |
| format | Article |
| id | doaj.art-a1f45abb611b4f5ea6fc5fd22319d749 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T19:47:19Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-a1f45abb611b4f5ea6fc5fd22319d7492022-12-22T04:06:27ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10387541038754Cannabidiol, ∆9-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS/MS following controlled administration in epilepsy patientsFederica Pigliasco0Sara Malaca1Alfredo Fabrizio Lo Faro2Anastasio Tini3Giuliana Cangemi4Alessia Cafaro5Alessia Cafaro6Sebastiano Barco7Antonella Riva8Angelica Pisati9Elisabetta Amadori10Pasquale Striano11Pasquale Striano12Adriano Tagliabracci13Marilyn Ann Huestis14Francesco Paolo Busardò15Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, ItalyDepartment of Excellence-Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, ItalyDepartment of Excellence-Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, ItalyDepartment of Excellence-Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, ItalyChromatography and Mass Spectrometry Section, Central Laboratory of Analyses, IRCCS Istituto Giannina Gaslini, Genoa, ItalyChromatography and Mass Spectrometry Section, Central Laboratory of Analyses, IRCCS Istituto Giannina Gaslini, Genoa, ItalyDepartment of Internal Medicine, Pharmacology & Toxicology Unit, University of Genoa, Genoa, ItalyChromatography and Mass Spectrometry Section, Central Laboratory of Analyses, IRCCS Istituto Giannina Gaslini, Genoa, ItalyDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, ItalyDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, ItalyDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, ItalyDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, ItalyPaediatric Neurology and Muscular Disease Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyDepartment of Excellence-Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, ItalyInstitute of Emerging Health Professions, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Excellence-Biomedical Sciences and Public Health, Università Politecnica delle Marche, Ancona, ItalyCannabidiol (CBD) exhibits anti-inflammatory, anxiolytic, antiseizure, and neuroprotective proprieties without addictive or psychotropic side effects, as opposed to Δ9-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-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-Δ9-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.https://www.frontiersin.org/articles/10.3389/fphar.2022.1038754/fullcannabinoidsmedical cannabisserumCBD metabolitesUHPLC-MS/MS |
| spellingShingle | Federica Pigliasco Sara Malaca Alfredo Fabrizio Lo Faro Anastasio Tini Giuliana Cangemi Alessia Cafaro Alessia Cafaro Sebastiano Barco Antonella Riva Angelica Pisati Elisabetta Amadori Pasquale Striano Pasquale Striano Adriano Tagliabracci Marilyn Ann Huestis Francesco Paolo Busardò Cannabidiol, ∆9-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS/MS following controlled administration in epilepsy patients Frontiers in Pharmacology cannabinoids medical cannabis serum CBD metabolites UHPLC-MS/MS |
| title | Cannabidiol, ∆9-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS/MS following controlled administration in epilepsy patients |
| title_full | Cannabidiol, ∆9-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS/MS following controlled administration in epilepsy patients |
| title_fullStr | Cannabidiol, ∆9-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS/MS following controlled administration in epilepsy patients |
| title_full_unstemmed | Cannabidiol, ∆9-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS/MS following controlled administration in epilepsy patients |
| title_short | Cannabidiol, ∆9-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS/MS following controlled administration in epilepsy patients |
| title_sort | cannabidiol ∆9 tetrahydrocannabinol and metabolites in human blood by volumetric absorptive microsampling and lc ms ms following controlled administration in epilepsy patients |
| topic | cannabinoids medical cannabis serum CBD metabolites UHPLC-MS/MS |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1038754/full |
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