{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:33:10Z","timestamp":1792153990076,"version":"4.4.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100007590","name":"Colorado Department of Public Health and Environment","doi-asserted-by":"publisher","award":["A Randomized, Double-blind, Placebo-controlled Cro"],"award-info":[{"award-number":["A Randomized, Double-blind, Placebo-controlled Cro"]}],"id":[{"id":"10.13039\/100007590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007590","name":"Colorado Department of Public Health and Environment","doi-asserted-by":"publisher","award":["Cannabidiol (CBD) and Pediatric Epilepsy (G.S. Wan"],"award-info":[{"award-number":["Cannabidiol (CBD) and Pediatric Epilepsy (G.S. Wan"]}],"id":[{"id":"10.13039\/100007590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007590","name":"Colorado Department of Public Health and Environment","doi-asserted-by":"publisher","award":["Use of Medicinal Cannabinoids as Adjunctive Treatm"],"award-info":[{"award-number":["Use of Medicinal Cannabinoids as Adjunctive Treatm"]}],"id":[{"id":"10.13039\/100007590","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In recent years, the surge in use of tetrahydrocannabinol (THC) and cannabidiol (CBD) has increased the need for sensitive and specific analytical assays to measure the said compounds in patients, to establish dose\u2013effect relationships and to gain knowledge of their pharmacokinetics and metabolism. We developed and validated an online extraction high-performance liquid chromatography-tandem mass spectrometry (HPLC\u2013MS-MS) method for simultaneous quantification of 17 cannabinoids and metabolites including THC and its metabolites, CBD and its metabolites and other minor cannabinoids in human plasma. CBD-glucuronide (CBD-gluc) standard was produced in-house by isolation of CBD-gluc from urine of patients using pure CBD oil. For calibration standards and quality control samples, human plasma was spiked with cannabinoids at varying concentrations within the working range of the respective compound and 200\u2009\u00b5L of the plasma was extracted using a simple one-step protein precipitation procedure. The extracts were analyzed using online trapping LC\/LC\u2013atmospheric pressure chemical ionization\u2013MS-MS running in the positive multiple reaction monitoring mode. The lower limit of quantification ranged from 0.78 to 7.8\u2009ng\/mL, and the upper limits of quantification were between 100 and 2,000\u2009ng\/mL. Inter-day analytical accuracy and imprecision ranged from 90.4% to 111% and from 3.1% to 17.4%, respectively. The analysis of plasma samples collected during clinical studies showed that (3R-trans)-cannabidiol-7-oic acid (7-CBD-COOH) was the major human metabolite with 5960% (59.6-fold) of CBD followed by 7-hydroxy-CBD (177%), CBD-gluc (157%) and 6\u03b1-hydroxy-CBD (39.8%); 6\u03b2-hydroxy-CBD was not detected in any of the samples. In the present study, we developed and validated a robust LC\u2013MS-MS assay for the simultaneous quantification of cannabinoids and their metabolites, which has been used to measure &amp;gt;5,000 samples in clinical studies. Moreover, we were able to quantify CBD-gluc and showed that 7-CBD-COOH, 7-hydroxy-CBD and CBD-gluc are the major CBD metabolites in human plasma.<\/jats:p>","DOI":"10.1093\/jat\/bkab030","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T20:10:55Z","timestamp":1616443855000},"page":"383-392","source":"Crossref","is-referenced-by-count":48,"title":["Simultaneous Quantification of 17 Cannabinoids by LC\u2013MS-MS in Human Plasma"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8095-612X","authenticated-orcid":false,"given":"Cristina","family":"Sempio","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nohemi","family":"Almaraz-Quinones","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanzhu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Sam","family":"Wang","sequence":"additional","affiliation":[{"name":"Section of Emergency Medicine and Medical Toxicology, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Children\u2019s Hospital Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Leehey","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Knupp","sequence":"additional","affiliation":[{"name":"Department of Neurology and Pediatrics, University of Colorado, Anschutz Medical Campus, Children\u2019s Hospital Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Klawitter","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Christians","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6413-4820","authenticated-orcid":false,"given":"Jost","family":"Klawitter","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"2022042108424489300_R1","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2019.00627","article-title":"Therapeutic prospects of cannabidiol for alcohol use disorder and alcohol-related damages on the liver and the brain","volume":"10","author":"De Ternay","year":"2019","journal-title":"Frontiers in Pharmacology"},{"key":"2022042108424489300_R2","article-title":"Cannabis and its secondary metabolites: their use as therapeutic drugs, toxicological aspects, and 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