title: Investigation of a recently detected THCCOOH isomer: Post mortem findings and comparison with Δ(8)-THCCOOH.
abstract: BACKGROUND
  An isomer of the non-psychoactive cannabinoid Δ(9)-THCCOOH was recently detected in blood from cannabis users. The structure of this compound is currently unknown. Therefore, further investigations were performed to elucidate its nature.
  
  
  METHODS
  Further biological specimens were analyzed using the previously published LC-MS/MS method to evaluate the distribution of this compound in the human body. Hypothetically, the unknown compound was isomeric in the position of the double bond, i.e. Δ(8)-THCCOOH. An in-vitro metabolism study on Δ(8)-THC and Δ(9)-THC was performed to compare the resulting metabolites with the unknown compound.
  
  
  RESULTS
  The unknown THCCOOH isomer was detected in all analyzed human body compartments (urine, bile, liver, lung and kidney) except for brain indicating that its detectability is not limited to blood. The in-vitro metabolism assay with the human CYP2C9 isoform led to the formation of THCOH and THCCOOH of Δ(8)-THC and Δ(9)-THC. However, the unknown isomer present in blood exhibited a different retention time than each of the metabolites formed.
  
  
  CONCLUSIONS
  The unknown THCCOOH isomer accompanied THCCOOH and was detected in various human body compartments. The present in-vitro metabolism study proved that it is not of Δ(8)-THCCOOH structure nor that it is metabolically formed by the human CYP2C9 isoform.
authors.affiliation: Institute of Legal Medicine, University of Frankfurt, Kennedyallee 104, D-60596 Frankfurt/Main, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hanisch
authors.affiliation: Institute of Legal Medicine, University of Frankfurt, Kennedyallee 104, D-60596 Frankfurt/Main, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Paulke
authors.affiliation: Institute of Legal Medicine, University of Frankfurt, Kennedyallee 104, D-60596 Frankfurt/Main, Germany. Electronic address: toennes@em.uni-frankfurt.de.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Toennes
mesh_terms: D001646:Bile / Q000737:chemistry; D001923:Brain Chemistry; D002186:Cannabinoids / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D015198:Designer Drugs / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D053593:Forensic Toxicology; D006801:Humans; D007536:Isomerism; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D013058:Mass Spectrometry; D011180:Postmortem Changes
chemical_list: D002186:Cannabinoids; D015198:Designer Drugs
keywords: CYP2C9; Cannabinoids; Drug testing; In-vitro metabolism; THCCOOH isomer