title: Determination of ∆-9-Tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC and Cannabidiol in Human Plasma using Gas Chromatography-Tandem Mass Spectrometry.
abstract: Two marijuana compounds of particular medical interest are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A gas chromatography-tandem mass spectrometry (GC-MS-MS) method was developed to test for CBD, THC, hydroxy-THC (OH-THC) and carboxy-THC (COOH-THC) in human plasma. Calibrators (THC and OH-THC, 0.1 to 100; CBD, 0.25 to 100; COOH-THC, 0.5-500 ng/mL) and controls (0.3, 5 and 80 ng/mL, except COOH-THC at 1.5, 25 and 400 ng/mL) were prepared in blank matrix. Deuterated (d3) internal standards were added to 1-mL samples. Preparation involved acetonitrile precipitation, liquid-liquid extraction (hexane:ethyl acetate, 9:1), and MSTFA derivatization. An Agilent 7890 A GC was interfaced with an Agilent 7000 MS Triple Quadrupole. Selected reaction monitoring was employed. Blood samples were provided from a marijuana smoking study (two participants) and a CBD ingestion study (eight participants). Three analytes with the same transitions (THC, OH-THC and COOH-THC) were chromatographically separated. Matrix selectivity studies showed endogenous chromatographic peak area ratios (PAR) at the analyte retention times were <20% of the analyte limit of quantitation PAR. The intra-assay accuracy ranged from 83.5% to 118% of target and the intra-run imprecision ranged from 2.0% to 19.1%. The inter-assay accuracy ranged from 90.3% to 104% of target and the inter-run imprecision ranged from 6.5% to 12.0%. Stability was established for 25 hours at room temperature, 207 days at -20°C, after three freeze-thaw cycles and for 26 days for rederivatized processed samples. After smoking marijuana predictable concentrations of THC, OH-THC and COOH-THC were seen; low concentrations of CBD were detected at early time points. In moderate users who had not smoked for at least 9 hours before ingesting an 800 mg oral dose of CBD, the method was sensitive enough to follow residual concentrations of THC and OH-THC; sustained COOH-THC concentrations over 50 ng/mL validated its higher analytical range.
authors.affiliation: Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Andrenyak
authors.affiliation: Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Moody
authors.affiliation: Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Slawson
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: O'Leary
authors.affiliation: Department of Psychiatry, Columbia UniversityMedical Center, New York City, NY, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Haney
mesh_terms: D002138:Calibration; D002185:Cannabidiol / Q000097:blood; D002186:Cannabinoids / Q000097:blood*; D013759:Dronabinol / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D013287:Illicit Drugs / Q000097:blood*; D008385:Marijuana Smoking; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D002186:Cannabinoids; D013287:Illicit Drugs; D002185:Cannabidiol; D013759:Dronabinol