title: Validation of the quantitative determination of tetrahydrocannabinol and its two major metabolites in plasma by ultra-high-performance liquid chromatography-tandem mass spectrometry according to the total error approach.
abstract: In Belgium, driving under the influence (DUI) of cannabis is prohibited and has severe legal consequences for the driver if the blood plasma concentration of Δ(9)-tetrahydrocannabinol (THC) exceeds 1 µg/L. A method to quantify low concentrations of THC and its hydroxylated (THC-OH) and carboxylated (THC-COOH) metabolites in plasma was developed for DUI but also for other applications. Ultra-high-performance liquid chromatography coupled to mass spectrometry seems to be a very convenient method to combine fast chromatographic separation and good sensitivity. The method was validated according to total error approach. Chromatographic separation was achieved in a 3-min total run time. The limits of quantitation were lower or equal to 1 µg/L for all compounds. The linearity of the method was acceptable in the validated range of concentrations (from 0.5 to 50 µg/L for THC, from 0.9 to 50 µg/L for THC-OH and from 1.1 to 100 µg/L for THC-COOH). The biases were lower than 13%, and the relative standard deviations for repeatability and intermediate precision did not exceed 15%. Lower and upper β-expectation tolerance limits did not exceed the acceptance limits of 20% for concentrations higher than 2 µg/L for THC and THC-OH and higher than 4 µg/L for THC-COOH. The acceptance limits were 30% for THC and THC-OH concentrations lower than 2 µg/L and for THC-COOH concentrations lower than 4 µg/L.
authors.affiliation: Service de Toxicologie Clinique, Médicolégale, de l'Environnement et en Entreprise, CHU, Liège, Belgium. nathalie.dubois@chu.ulg.ac.be
authors.forename: N
authors.initials: N
authors.lastname: Dubois
authors.forename: A P
authors.initials: AP
authors.lastname: Paccou
authors.forename: B G
authors.initials: BG
authors.lastname: De Backer
authors.forename: C J
authors.initials: CJ
authors.lastname: Charlier
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D013759:Dronabinol / Q000097:blood* / Q000378:metabolism; D006801:Humans; D057230:Limit of Detection; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D013759:Dronabinol