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An increasing number of preclinical studies and clinical trials have been conducted with one or both compounds, often probing their therapeutic effects in conditions such as paediatric epilepsy, anxiety disorders or chronic pain. Accurate monitoring of THC and CBD and their metabolites is essential for tracking treatment adherence and pharmacokinetics. However, fully validated methods for the comprehensive analysis of major Phase I CBD metabolites are yet to be developed due to a historical lack of commercially available reference material. In the present study, we developed, optimised and validated a method for the simultaneous quantification of CBD, THC and their major Phase I metabolites 6\u2010hydroxy\u2010CBD (6\u2010OH\u2010CBD), 7\u2010hydroxy\u2010CBD (7\u2010OH\u2010CBD), 7\u2010carboxy\u2010CBD (7\u2010COOH\u2010CBD), 11\u2010hydroxy\u2010tetrahydrocannabinol (11\u2010OH\u2010THC) and 11\u2010carboxy\u2010tetrahydrocannabinol (11\u2010COOH\u2010THC) as per Food and Drug Administration (FDA) guidelines for bioanalytical method validation. The method is accurate, reproducible, sensitive and can be carried out in high\u2010throughput 96\u2010well formats, ideal for larger scale clinical trials. Deuterated internal standards for each analyte were crucial to account for variable matrix effects between plasma lots. The application of the method to plasma samples, taken from people who had been administered oral CBD as part of an open\u2010label trial of CBD effects in anxiety disorders, demonstrated its immediate utility in ongoing and upcoming clinical trials. The method will prove useful for future studies involving CBD and\/or THC and can likely accommodate the inclusion of additional metabolites as analytical reference materials become commercially available.<\/jats:p>","DOI":"10.1002\/dta.2947","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T13:37:26Z","timestamp":1603460246000},"page":"614-627","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["A validated method for the simultaneous quantification of cannabidiol, \u0394<sup>9<\/sup>\u2010tetrahydrocannabinol, and their metabolites in human plasma and application to plasma samples from an oral cannabidiol open\u2010label trial"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4912-4499","authenticated-orcid":false,"given":"Richard C.","family":"Kevin","sequence":"first","affiliation":[{"name":"School of Psychology, Faculty of Science The University of Sydney  Sydney New South Wales Australia"},{"name":"The Lambert Initiative for Cannabinoid Therapeutics, Brain and Mind Centre The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Vogel","sequence":"additional","affiliation":[{"name":"The Lambert Initiative for Cannabinoid Therapeutics, Brain and Mind Centre The University of Sydney  Sydney New South Wales Australia"},{"name":"School of Chemistry, Faculty of Science The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Doohan","sequence":"additional","affiliation":[{"name":"The Lambert Initiative for Cannabinoid Therapeutics, Brain and Mind Centre The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximus","family":"Berger","sequence":"additional","affiliation":[{"name":"Orygen Youth Health  Melbourne Victoria Australia"},{"name":"Centre for Youth Mental Health University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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