title: Mass spectral studies on 1-n-pentyl-3-(1-naphthoyl)indole (JWH-018), three deuterium-labeled analogues and the inverse isomer 1-naphthoyl-3-n-pentylindole.
abstract: BACKGROUND
  A number of synthetic cannabinoids such as the 1-alkyl-3-acylindoles are the target of significant designer drug activity. One of the first waves of these compounds identified in clandestine samples was 1-n-pentyl-3-(1-naphthoyl)indole, JWH-018. These totally synthetic molecules can be prepared in a number of regioisomeric forms.
  
  
  METHODS
  The electron ionization mass spectrometric (EI-MS) fragmentation of the 1-n-pentyl-3-(1-naphthoyl)indole is compared to its inverse isomer 1-naphthoyl-3-n-pentylindole. These two substances are directly available from indole using identical precursor reagents and similar reaction conditions. Stable isotope deuterium labeling of the three major regions of the JWH-018 molecule allows confirmation of the structures of the major fragment ions. The spectra for the 1-n-pentyl-3-(1-naphthoyl)-d(5) -indole, 1-n-pentyl-3-(1-d(7) -naphthoyl)indole and 1-d(11) -n-pentyl-3-(1-naphthoyl)indole provide significant assistance in elucidating the structures for the major fragment ions in JWH-018.
  
  
  RESULTS
  The EI mass spectra for these isomers show a number of unique ions which allow for the differentiation of the 1-alkyl-3-acylindole compounds from the inverse regioisomeric 1-acyl-3-alkylindoles. The fragment ion [M-17](+) at m/z 324 for JWH-018 was formed by the elimination of a hydroxyl radical and the spectra of the three deuterium-labeled derivatives indicated the loss of hydrogen from the naphthalene ring. Further structural analogues suggest the hydrogen to come from the 8-position of the naphthalene ring.
  
  
  CONCLUSIONS
  The three deuterium-labeled analogues provide significant assistance in confirming the structures for the major fragment ions in the mass spectrum of the traditional synthetic cannabinoid compound, 1-n-pentyl-3-(1-naphthoyl)indole, JWH-018. The 1-naphthoyl-3-n-pentylindole inverse regioisomer can be easily differentiated from the traditional synthetic cannabinoid compound.
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Thaxton
authors.affiliation: Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
authors.forename: Tarek S
authors.initials: TS
authors.lastname: Belal
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.
authors.forename: Forrest
authors.initials: F
authors.lastname: Smith
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: DeRuiter
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.|Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
authors.forename: Karim M
authors.initials: KM
authors.lastname: Abdel-Hay
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.
authors.forename: C Randall
authors.initials: CR
authors.lastname: Clark
mesh_terms: D002186:Cannabinoids / Q000737:chemistry*; D015198:Designer Drugs / Q000737:chemistry*; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D007211:Indoles / Q000737:chemistry*; D007536:Isomerism; D009281:Naphthalenes / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D002186:Cannabinoids; D015198:Designer Drugs; D007211:Indoles; D009281:Naphthalenes; D003903:Deuterium; C552597:1-pentyl-3-(1-naphthoyl)indole