Liquid chromatography-tandem mass spectrometry analysis of urine specimens for K2 (JWH-018) metabolites

Abstract

Marijuana is the most widely used drug of abuse all over the world. The major active constituent of the drug is Δ9-tetrahydrocannabinol (Δ9-THC). Δ9-THC exerts its psychological activities by interacting with the cannabinoid receptors (CB1 and CB2) in the brain. JWH-018, HU-210, and CP-47497, with CB1 agonist activity (similar to Δ9-THC), have been used by the drug culture to spike smokable herbal products to attain psychological effects similar to those obtained by smoking marijuana. The products spiked with these CB1 agonists are commonly referred to as "Spice" or "K2". The most common compound used in these products is JWH-018 and related compounds (JWH-073 and JWH- 250). Little work has been done on the detection of these synthetic cannabimimetic compounds in biological specimens. This report investigated the metabolism of JWH-018 by human liver microsomes, identification of the metabolites of JWH-018 in urine specimen of an individual who admitted use of the drug, and reports on the quantitation of three of its urinary metabolites, namely the 6-OH-, the N-alkyl OH (terminal hydroxyl)-, and the N-alkyl terminal carboxy metabolites using liquid chromatography-tandem mass spectrometry. The concentrations of these metabolites are determined in several forensic urine specimens.