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Title: On-Line Solid Phase Extraction High Performance Liquid Chromatography Method Coupled With Tandem Mass Spectrometry for the Therapeutic Monitoring of Cannabidiol and 7-Hydroxy-cannabidiol in Human Serum and Saliva.
Austin Authors: Franco, Valentina;Palmisani, Michela;Marchiselli, Roberto;Crema, Francesca;Fattore, Cinzia;De Giorgis, Valentina;Varesio, Costanza;Rota, Paola;Dibari, Vincenza Flora;Perucca, Emilio
Affiliation: Department of Internal Medicine and Therapeutics, Clinical and Experimental Pharmacology Unit, University of Pavia, Pavia, Italy..
IRCCS Mondino Foundation, Pavia, Italy..
Department of Internal Medicine and Therapeutics, Clinical and Experimental Pharmacology Unit, University of Pavia, Pavia, Italy..
Department of Neuroscience, Monash University, Melbourne, VIC, Australia..
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy..
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy..
B.S.N. Srl R&D Laboratory, Castelleone, Italy..
Medicine (University of Melbourne)
Issue Date: 22-Jun-2022
Date: 2022
Publication information: Frontiers in pharmacology 2022; 13: 915004
Abstract: Cannabidiol is a novel antiseizure medication approved in Europe and the US for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome and tuberous sclerosis complex. We describe in this article a new and simple liquid chromatography-mass spectrometry method (LC-MS/MS) for the determination of cannabidiol and its active metabolite 7-hydroxy-cannabidiol in microvolumes of serum and saliva (50 μl), to be used as a tool for therapeutic drug monitoring (TDM) and pharmacokinetic studies. After on-line solid phase extraction cannabidiol, 7-hydroxy-cannabidiol and the internal standard cannabidiol-d3 are separated on a monolithic C18 column under gradient conditions. Calibration curves are linear within the validated concentration range (10-1,000 ng/ml for cannabidiol and 5-500 ng/ml for 7-hydroxy-cannabidiol). The method is accurate (intraday and interday accuracy within 94-112% for cannabidiol, 91-109% for 7-hydroxy-cannabidiol), precise (intraday and interday precision <11.6% for cannabidiol and <11.7% for 7- hydroxy-cannabidiol) and sensitive, with a LOQ of 2.5 ng/ml for cannabidiol and 5 ng/ml for 7-hydroxy-cannabidiol. The stability of the analytes was confirmed under different storage conditions. Extraction recoveries were in the range of 81-129% for cannabidiol and 100-113% for 7-hydroxy-cannabidiol. The applicability of the method to TDM was demonstrated by analysis of human serum and saliva samples obtained from patients with epilepsy treated with cannabidiol.
DOI: 10.3389/fphar.2022.915004
ORCID: 0000-0003-3232-1389
Journal: Frontiers in pharmacology
PubMed URL: 35814197
PubMed URL:
ISSN: 1663-9812
Type: Journal Article
Subjects: 7-hydroxy-cannabidiol
antiseizure medications
on-line solid phase extraction
Appears in Collections:Journal articles

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