title: Simultaneous quantification of Delta9-tetrahydrocannabinol, 11-hydroxy-Delta9-tetrahydrocannabinol, and 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in human plasma using two-dimensional gas chromatography, cryofocusing, and electron impact-mass spectrometry.
abstract: A two-dimensional (2D) gas chromatography/electron impact-mass spectrometry (GC/EI-MS) method for simultaneous quantification of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC), and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in human plasma was developed and validated. The method employs 2D capillary GC and cryofocusing for enhanced resolution and sensitivity. THC, 11-OH-THC, and THCCOOH were extracted by precipitation with acetonitrile followed by solid-phase extraction. GC separation of trimethylsilyl derivatives of analytes was accomplished with two capillary columns in series coupled via a pneumatic Deans switch system. Detection and quantification were accomplished with a bench-top single quadrupole mass spectrometer operated in electron impact-selected ion monitoring mode. Limits of quantification (LOQ) were 0.125, 0.25 and 0.125 ng/mL for THC, 11-OH-THC, and THCCOOH, respectively. Accuracy ranged from 86.0 to 113.0% for all analytes. Intra- and inter-assay precision, as percent relative standard deviation, was less than 14.1% for THC, 11-OH-THC, and THCCOOH. The method was successfully applied to quantification of THC and its 11-OH-THC and THCCOOH metabolites in plasma specimens following controlled administration of THC.
authors.affiliation: Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: Ross H
authors.initials: RH
authors.lastname: Lowe
authors.forename: Erin L
authors.initials: EL
authors.lastname: Karschner
authors.forename: Eugene W
authors.initials: EW
authors.lastname: Schwilke
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Barnes
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D002849:Chromatography, Gas / Q000379:methods*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D015203:Reproducibility of Results
chemical_list: C001427:11-hydroxy-delta(9)-tetrahydrocannabinol; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol