Department of Pharmacology and Therapeutics, Trinity College, School of Medicine, Dublin 8, Ireland.
J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Sep 1;934:102-8. doi: 10.1016/j.jchromb.2013.07.005. Epub 2013 Jul 15.
The synthetic phenylacetylindole cannabimimetics, JWH-203 and JWH-251, have been identified in 'herbal' smoking mixtures following the widespread legislative control of 'first generation' compounds such as JWH-018 and CP47, 497(C8). N-Alkylindole cannabimimetics (including phenylacetylindoles) undergo extensive metabolism and little or none of the parent compounds are found in urine. Utilizing GC-MS and LC-MS/MS, a series of JWH-203 and JWH-251 urinary metabolites have been tentatively identified. These are products of mono- and dihydroxylation, monohydroxylation combined with formation of carbonyl group on the N-pentyl chain, carboxylation of N-pentyl chain and N-dealkylation combined with monohydroxylation. Additionally, trihydroxylated metabolites were detected for JWH-203. No parent compounds were detected. The monohydroxylated metabolites with the hydroxyl group positioned on the N-pentyl chain were the most abundant and were found to be suitable for establishing ingestion of JWH-203 or JWH-250. Maximum urinary concentrations of chain-monohydroxylated metabolites were observed at 2.5-3h (JWH-203) and 6-10h (JWH-251) following ingestion. These metabolites were observed (GC-MS) for to 10 and 8 days (JWH-203 and JWH-251, respectively).
合成苯乙酰吲哚类大麻类似物 JWH-203 和 JWH-251 在“草药”吸烟混合物中被发现，此前“第一代”化合物（如 JWH-018 和 CP47,497(C8)）受到广泛的立法管制。N-烷基吲哚类大麻类似物（包括苯乙酰吲哚类）经历广泛的代谢，尿液中几乎检测不到母体化合物。利用 GC-MS 和 LC-MS/MS，初步鉴定了一系列 JWH-203 和 JWH-251 的尿代谢产物。这些是单羟基化和二羟基化、N-戊基链上形成羰基的单羟基化结合、N-戊基链的羧化以及 N-脱烷基化与单羟基化结合的产物。此外，还检测到 JWH-203 的三羟基化代谢产物。未检测到母体化合物。具有 N-戊基链上羟基的单羟基化代谢物最为丰富，被发现适合于建立 JWH-203 或 JWH-250 的摄入。摄入后 2.5-3 小时（JWH-203）和 6-10 小时（JWH-251）观察到链单羟基化代谢物的最大尿浓度。这些代谢物在 10 天和 8 天（JWH-203 和 JWH-251）内（GC-MS）被观察到。
