title: Determination of naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in mouse blood and tissue after inhalation exposure to 'buzz' smoke by HPLC/MS/MS.
abstract: The disposition of the cannabimimetic naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in mice following inhalation of the smoke of the herbal incense product (HIP) 'Buzz' is presented. A high-pressure liquid chromatography with electrospray ionization triple quadrupole mass spectrometer (HPLC/MS/MS) method was validated for the analysis of JWH-018 in the specimens using deuterated Δ(9) -tetrahydrocannabinol (d(3) -THC) as the internal standard. JWH-018 was isolated by cold acetonitrile liquid-liquid extraction. Chromatographic separation was performed on a Zorbaz eclipse XDB-C(18) column. The assay was linear from 1 to 1000 ng/mL. Six C57BL6 mice were sacrificed 20 min after exposure to the smoke of 200 mg 'Buzz' containing 5.4% JWH-018. Specimen concentrations of JWH-018 were: blood, 54-166 ng/mL (mean 82 ± 42 ng/mL); brain, 316-708 ng/g (mean 510 ± 166 ng/g); and liver, 1370-3220 ng/mL (mean 1990 ± 752 ng/mL). The mean blood to brain ratio for JWH-018 was 6.8 and ranged from 4.2 to 10.9. After exposure, the responses of the mice were consistent with cannabinoid receptor type 1 activity: body temperatures dropped 7.3 ± 1.1 °C, and catalepsy, hyperreflexia, straub tail and ptosis were observed. The brain concentrations and physiological responses are consistent with the hypothesis that the behavioral effects of 'Buzz' are attributable to JWH-018.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA USA. jlpoklis@vcu.edu
authors.forename: Justin L
authors.initials: JL
authors.lastname: Poklis
authors.forename: Dorra
authors.initials: D
authors.lastname: Amira
authors.forename: Laura E
authors.initials: LE
authors.lastname: Wise
authors.forename: Jason M
authors.initials: JM
authors.lastname: Wiebelhaus
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Haggerty
authors.forename: Aron H
authors.initials: AH
authors.lastname: Lichtman
authors.forename: Alphonse
authors.initials: A
authors.lastname: Poklis
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015198:Designer Drugs / Q000008:administration & dosage* / Q000737:chemistry; D013759:Dronabinol; D013287:Illicit Drugs / Q000032:analysis; D007211:Indoles / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D016014:Linear Models; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009281:Naphthalenes / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D012906:Smoke; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D015198:Designer Drugs; D013287:Illicit Drugs; D007211:Indoles; D009281:Naphthalenes; D012906:Smoke; D013759:Dronabinol; C552597:1-pentyl-3-(1-naphthoyl)indole