Targeted metabolomic approach for assessing human synthetic cannabinoid exposure and pharmacology

Amy L. Patton, Kathryn A. Seely, Krishna C. Chimalakonda, Johnny P. Tran, Matthew Trass, Art Miranda, William E. Fantegrossi, Paul D. Kennedy, Paul Dobrowolski, Anna Radominska-Pandya, Keith R. McCain, Laura P. James, Gregory W. Endres, Jeffery H. Moran

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Designer synthetic cannabinoids like JWH-018 and AM2201 have unique clinical toxicity. Cytochrome-P450-mediated metabolism of each leads to the generation of pharmacologically active (ω)- and (ω-1)-monohydroxyl metabolites that retain high affinity for cannabinoid type-1 receptors, exhibit Δ9-THC-like effects in rodents, and are conjugated with glucuronic acid prior to excretion in human urine. Previous studies have not measured the contribution of the specific (ω-1)-monohydroxyl enantiomers in human metabolism and toxicity. This study uses a chiral liquid chromatography-tandem mass spectroscopy approach (LC-MS/MS) to quantify each specific enantiomer and other nonchiral, human metabolites of JWH-018 and AM2201 in human urine. The accuracy (average % RE = 18.6) and reproducibility (average CV = 15.8%) of the method resulted in low-level quantification (average LLQ = 0.99 ng/mL) of each metabolite. Comparisons with a previously validated nonchiral method showed strong correlation between the two approaches (average r2 = 0.89). Pilot data from human urine samples demonstrate enantiospecific excretion patterns. The (S)-isomer of the JWH-018-(ω-1)- monohydroxyl metabolite was predominantly excreted (>87%) in human urine as the glucuronic acid conjugate, whereas the relative abundance of the corresponding AM2201-(ω-1)-metabolite was low (<5%) and did not demonstrate enantiospecificity (approximate 50:50 ratio of each enantiomer). The new chiral method provides a comprehensive, targeted metabolomic approach for studying the human metabolism of JWH-018 and AM2201. Preliminary evaluations of specific enantiomeric contributions support the use of this approach in future studies designed to understand the pharmacokinetic properties of JWH-018 and/or AM2201.

Original languageEnglish (US)
Pages (from-to)9390-9399
Number of pages10
JournalAnalytical Chemistry
Volume85
Issue number19
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry

Fingerprint

Dive into the research topics of 'Targeted metabolomic approach for assessing human synthetic cannabinoid exposure and pharmacology'. Together they form a unique fingerprint.

Cite this