{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:26:01Z","timestamp":1785763561880,"version":"3.56.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Cannabidiol (CBD) exhibits anti-inflammatory, anxiolytic, antiseizure, and neuroprotective proprieties without addictive or psychotropic side effects, as opposed to \u0394<jats:sup>9<\/jats:sup>-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-\u03b1-OH-CBD); and 6-beta-hydroxycannabidiol (6-\u03b2-OH-CBD); 11- Hydroxy-\u0394<jats:sup>9<\/jats:sup>-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-\u0394<jats:sup>9<\/jats:sup>-tetrahydrocannabinol (THCCOOH). After overnight enzymatic glucuronide hydrolysis at 37\u00b0C, 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\u201325 THC, 11-OH-THC, THCCOOH, 6-\u03b1-OH-CBD and 6-\u03b2-OH-CBD; 10\u2013500 CBD and 7-OH-CBD; and 20\u20135000 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\u00a0\u00b5L blood.<\/jats:p>","DOI":"10.3389\/fphar.2022.1038754","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T05:37:40Z","timestamp":1666589860000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Cannabidiol, \u22069-tetrahydrocannabinol, and metabolites in human blood by volumetric absorptive microsampling and LC-MS\/MS following controlled administration in epilepsy patients"],"prefix":"10.3389","volume":"13","author":[{"given":"Federica","family":"Pigliasco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Malaca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo Fabrizio","family":"Lo Faro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasio","family":"Tini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Cangemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Cafaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiano","family":"Barco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Riva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Pisati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Amadori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Tagliabracci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn Ann","family":"Huestis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Paolo","family":"Busard\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1684\/epd.2020.1141","article-title":"Epilepsy and cannabidiol: A guide to treatment","volume":"22","author":"Arzimanoglou","year":"2020","journal-title":"Epileptic Disord."},{"key":"B2","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.jpba.2017.07.033","article-title":"Volumetric adsorptive microsampling-liquid chromatography tandem mass spectrometry assay for the simultaneous quantification of four antibiotics in human blood: Method development validation and comparison with dried blood spot","volume":"145","author":"Barco","year":"2017","journal-title":"J. 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