LC/MS/MS Analysis of Urine Specimens for K2 (JWH-018) Metabolites

Marijuana is the most widely used drug of abuse all over the world. The 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 [1]. JWH-018 (1), HU-210 (2), and CP-47, 497 (3), 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 (1) and related compounds [(JWH-073 (4) and JWH-250 (5)]. While spice or K2 (JWH-018 and related compounds) have been banned in many European countries, it remains uncontrolled at the federal level in the USA. However, some states have enacted legislations prohibiting the sale of these products, with other states having legislations pending. Little work has been done on the detection of these synthetic cannabinimetic compounds in biological specimens. This report investigated the metabolism of JWH-018 by human liver microsomes, investigation of the metabolites of JWH-018 in urine specimen of an individual who admitted use of the drug, and reports the quantitation of three of its urinary metabolites of the drug, namely the 6-OH-, the N-alkyl OH (terminal hydroxyl)- and the N-alkyl terminal carboxy metabolites using state of art LC/MS/MS. Reference: [1] Raymon PL, Walls CH, (2007) Pharmacology of Cannabinoids, Chapter 5, 97–123 in Marijuana and the Cannabinoids, Humana Press.