title: Solid-phase extraction and quantitative measurement of omega and omega-1 metabolites of JWH-018 and JWH-073 in human urine.
abstract: The aminoalkylindole agonists JWH-018 and JWH-073 are contained in "K2/SPICE" products sold as "legal marijuana". Previous human metabolic studies have identified (ω)-hydroxyl and (ω)-carboxyl metabolites as biomarkers that are indicative of product use. However, other primary metabolites exhibiting similar chromatographic properties and mass spectra are also excreted in human urine. Analytical standards were used in this study to identify new primary metabolites as (ω-1)-hydroxyl derivatives of JWH-018 and JWH-073. The liquid chromatography tandem mass spectrometry (LC-MS/MS) procedure, coupled with an automated solid-phase extraction procedure incorporating deuterium-labeled internal standards, provides rapid resolution of the (ω)- and (ω-1) metabolites with adequate sensitivity, precision, and accuracy for trace analysis in human urine. Results from four urine specimens collected after individuals reportedly self-administered either JWH-018 or a mixture of JWH-018 and JWH-073 showed the following: (1) all tested metabolites were excreted in high concentrations, (2) (ω)- and (ω-1)-hydroxyl metabolites were exclusively excreted as glucuronic acid conjugates, and (3) ∼5%-80% of the (ω)-carboxyl metabolites was excreted as glucuronic acid conjugates. This is the first report to identify and quantify (ω-1)-hydroxyl metabolites of JWH-018 and JWH-073 and the first to incorporate automated extraction procedures using deuterium-labeled internal standards. Full clinical validation awaits further testing.
authors: Department of Pharmacology & Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States.
authors: Krishna C
authors: KC
authors: Chimalakonda
authors: Cindy L
authors: CL
authors: Moran
authors: Paul D
authors: PD
authors: Kennedy
authors: Gregory W
authors: GW
authors: Endres
authors: Adam
authors: A
authors: Uzieblo
authors: Paul J
authors: PJ
authors: Dobrowolski
authors: E Kim
authors: EK
authors: Fifer
authors: Jeff
authors: J
authors: Lapoint
authors: Lewis S
authors: LS
authors: Nelson
authors: Robert S
authors: RS
authors: Hoffman
authors: Laura P
authors: LP
authors: James
authors: Anna
authors: A
authors: Radominska-Pandya
authors: Jeffery H
authors: JH
authors: Moran
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D003903:Deuterium / Q000737:chemistry; D006801:Humans; D013287:Illicit Drugs / Q000652:urine*; D007211:Indoles / Q000652:urine*; D009281:Naphthalenes / Q000652:urine*; D012015:Reference Standards; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods*; D013194:Staining and Labeling; D015813:Substance Abuse Detection / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D013287:Illicit Drugs; D007211:Indoles; D009281:Naphthalenes; D003903:Deuterium; C552597:1-pentyl-3-(1-naphthoyl)indole