title: Metabolism of RCS-8, a synthetic cannabinoid with cyclohexyl structure, in human hepatocytes by high-resolution MS.
abstract: BACKGROUND
  Since 2008, synthetic cannabinoids are major new designer drugs of abuse. They are extensively metabolized and excreted in urine, but limited human metabolism data are available. As there are no reports on the metabolism of RCS-8, a scheduled phenylacetylindole synthetic cannabinoid with an N-cyclohexylethyl moiety, we investigated metabolism of this new designer drug by human hepatocytes and high resolution MS.
  
  
  METHODS
  After human hepatocyte incubation with RCS-8, samples were analyzed on a TripleTOF 5600+ mass spectrometer with time-of-flight survey scan and information-dependent acquisition triggered product ion scans. Data mining of the accurate mass full scan and product ion spectra employed different data processing algorithms.
  
  
  CONCLUSIONS
  More than 20 RCS-8 metabolites were identified, products of oxidation, demethylation, and glucuronidation. Major metabolites and targets for analytical methods were hydroxyphenyl RCS-8 glucuronide, a variety of hydroxycyclohexyl-hydroxyphenyl RCS-8 glucuronides, hydroxyphenyl RCS-8, as well as the demethyl-hydroxycyclohexyl RCS-8 glucuronide.
authors.affiliation: Chemistry & Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Biomedical Research Center, 251 Bayview Boulevard Suite 200 Room 05A-721, Baltimore, MD 21224, USA.
authors.forename: Ariane
authors.initials: A
authors.lastname: Wohlfarth
authors.forename: Shaokun
authors.initials: S
authors.lastname: Pang
authors.forename: Mingshe
authors.initials: M
authors.lastname: Zhu
authors.forename: Adarsh S
authors.initials: AS
authors.lastname: Gandhi
authors.forename: Karl B
authors.initials: KB
authors.lastname: Scheidweiler
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D002186:Cannabinoids / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D003510:Cyclohexanes / Q000737:chemistry* / Q000378:metabolism; D022781:Hepatocytes / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry
chemical_list: D002186:Cannabinoids; D003510:Cyclohexanes; D007211:Indoles; C000596114:1-(2-cyclohexylethyl)-3-(2-methoxyphenylacetyl)indole