Identification of analogs of LY2183240 and the LY2183240 2′-isomer in herbal products

LY2183240 and the LY2183240 2′-isomer inhibit cellular reuptake and enzymatic hydrolysis of endocannabinoids. These compounds were detected in herbal blend products as designer drugs. Simultaneously, two analogs of LY2183240 and LY2183240 2′-isomer were also detected; (A) 5-[(biphenyl-4-yl)methyl]-1H-tetrazole and (B) 2-(N,N-dimethylamino)-5-[(biphenyl-4-yl)methyl]-1,3,4-oxadiazole. The structure of compound B was identified by nuclear magnetic resonance spectroscopy and X-ray crystallography. To reveal the mechanism of production of these compounds in herbal products, we analyzed the reference standard solution of LY2183240 or the LY2183240 2′-isomer after treatment under various conditions. Compound A was easily formed as a decomposition product of both LY2183240 and the LY2183240 2′-isomer under hydrolysis conditions. Compound B was only detected from the solution of the LY2183240 2′-isomer. These findings suggest that compound B was produced by elimination of N₂ from the tetrazole structure; LY2183240 and the LY2183240 2′-isomer may be decomposed at the step of producing herbal blend products, extraction procedure, and/or instrumental analysis. This is the first report to reveal the presence of two analogs of LY2183240 or the LY2183240 2′-isomer in herbal blend products.