Structure characterisation of urinary metabolites of the cannabimimetic JWH-018 using chemically synthesised reference material for the support of LC-MS/MS-based drug testing

  title={Structure characterisation of urinary metabolites of the cannabimimetic JWH-018 using chemically synthesised reference material for the support of LC-MS/MS-based drug testing},
  author={Simon Beuck and Ines M{\"o}ller and Andreas Thomas and Annika Klose and Nils E. Schl{\"o}rer and Wilhelm Schänzer and Mario Thevis},
  journal={Analytical and Bioanalytical Chemistry},
AbstractAs recently reported, the synthetic cannabinoid JWH-018 is the subject of extensive phase I and II metabolic reactions in vivo. Since these studies were based on LC-MS/MS and/or GC-MS identification and characterisation of analytes, the explicit structural assignment of the metabolites was only of preliminary nature, if possible at all. Here, we report the chemical synthesis of five potential in vivo metabolites of JWH-018 derivatives featuring an alkylcarboxy (M1), a terminal… 
Characterization of in vitro metabolites of JWH-018, JWH-073 and their 4-methyl derivatives, markers of the abuse of these synthetic cannabinoids.
  • V. Gambaro, S. Arnoldi, E. Valoti
  • Chemistry
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
  • 2014
Development of a mass spectrometric hydroxyl-position determination method for the hydroxyindole metabolites of JWH-018 by GC-MS/MS.
Analysis of the fragmentation patterns suggests that the present method has high potential to be extended to hydroxyindole metabolites of other naphthoylindole type SCs in identifying the position of the hydroxyl group on the indole ring.
Qualitative confirmation of 9 synthetic cannabinoids and 20 metabolites in human urine using LC-MS/MS and library search.
A qualitative LC-MS/MS method identifying urinary metabolites of synthetic cannabinoids and their parent compounds was presented, fully validated, including proof of selectivity and assessment of matrix effects.
Identification of the major urinary metabolites in man of seven synthetic cannabinoids of the aminoalkylindole type present as adulterants in 'herbal mixtures' using LC-MS/MS techniques.
The identification of the major metabolites of the currently most common seven synthetic cannabinoids is presented and these results facilitate the design of urine screening methods for detecting consumption of synthetic cannabinoids.
Conjugation of Synthetic Cannabinoids JWH-018 and JWH-073, Metabolites by Human UDP-Glucuronosyltransferases
Nine human recombinant uridine diphosphate-glucuronosyltransferase (UGT) isoforms and human liver and intestinal microsomes are evaluated for their ability to glucuronidate hydroxylated metabolites of K2, which indicates that K2 metabolites may be rapidly glucuronidated and eliminated from the body.
The detection of the urinary metabolites of 1-[(5-fluoropentyl)-1H-indol-3-yl]-(2-iodophenyl)methanone (AM-694), a high affinity cannabimimetic, by gas chromatography - mass spectrometry.
Using gas chromatography-mass spectrometry (GC-MS), six metabolites were identified in post-ingestion samples of AM-694, a synthetic indole-based cannabimimetic, and one metabolite (a product of hydrolytic defluorination) was also identified in urine samples from two individuals admitted to hospital suffering from suspected drug overdoses.
Detection of urinary metabolites of AM-2201 and UR-144, two novel synthetic cannabinoids.
In vitro and in vivo metabolism of AM-2201 and forensic urine samples were analyzed and it has been shown that for both cannabimimetics the recommended screening targets are the monohydroxylated metabolites.
In vivo and in vitro metabolism of the synthetic cannabinoid JWH-200.
The metabolite formed by consecutive morpholine cleavage and oxidation of the remaining side chain to a carboxylic group was detected in the highest amounts with the longest detection time and is the best candidate metabolite to detect JWH-200 abuse in urine.


In vitro phase I metabolism of the synthetic cannabimimetic JWH-018
The cytochrome P450 phase I metabolites of JWH-018 were investigated, after in vitro incubation of the drug with human liver microsomes followed by liquid chromatography–tandem mass spectrometry analysis, and evidence of trihydroxylation at different locations of the hydroxyl groups in the molecule was found.
Detection of JWH-018 metabolites in smoking mixture post-administration urine.
Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls.
A urine sample of a healthy man declaring to have smoked a 'spice' product was screened for potential phase-I and -II metabolites by high-resolution/high-accuracy mass spectrometry and demonstrated its capability for a sensitive and selective identification of JWH-018 and its metabolites in human urine.
Screening for unknown synthetic steroids in human urine by liquid chromatography-tandem mass spectrometry.
Characteristic product ions were selected to serve as diagnostic markers for previously unidentified drugs or drug metabolites in human urine samples and provided structural identification of the unknown compounds.
Matrix effect in bio-analysis of illicit drugs with LC-MS/MS: Influence of ionization type, sample preparation, and biofluid
Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS.
Practical, experimental approaches for studying, identifying, and eliminating the effect of matrix on the results of quantitative analyses by HPLC-MS/MS are described and it is demonstrated that, for the investigational drug under study, the matrix effect was clearly observed when ISP interface was utilized but it was absent when the HN interface was employed.