Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls
Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls
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DOI：
10.1002/dta.158
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发表时间：
2011-09-01
影响因子：
2.9
通讯作者：
Thevis, Mario
中科院分区：
文献类型：
--
作者：
Moeller, Ines;Wintermeyer, Annette;Thevis, Mario
在过去几年中，市场上出现了几种被称为“香料”的新药，广告宣传为草药混合物，其中合成大麻素JWH-018和CP 47，497的C（8）同系物被确定为主要活性成分。由于其报告的大麻样作用，许多欧洲国家已经禁止这些物质。世界反兴奋剂机构也明确禁止在精英体育比赛中使用合成大麻素。由于尿液样本一直是首选的兴奋剂控制样本，因此阐明这些物质的代谢途径对于在体育药物检测计划中实施这些物质尤为重要。在最近的一份报告中，介绍了JWH-018的体外I期代谢研究，主要产生羟基化和N-脱烷基化代谢产物。由于这些发现，一个健康的人的尿液样本声称已吸烟的“香料”产品进行了筛选潜在的第一阶段和第二阶段的代谢物的高分辨率/高精度质谱在本报告中。在该尿液标本中检测到JWH-018早期体外研究中观察到的大多数I相代谢产物，此外还检测到其各自的大多数单葡糖苷酸。由于无法检测到完整的JWH-018，因此选择最丰富的单羟基化代谢物作为运动药物检测目的的目标分析物;随后根据基于酶水解、液-液萃取和液相色谱/电喷雾串联质谱分析的常规筛选方案开发并验证了检测方法。该方法应用于约7500尿液兴奋剂控制样品产生两个JWH-018的结果，并证明了其灵敏度和选择性鉴定人尿液中的JWH-018及其代谢物的能力。版权所有（C）2010约翰威利父子有限公司
Referred to as 'spice', severalnewdrugs, advertised as herbalblends, have appeared on the market in the last few years, in which the synthetic cannabinoids JWH-018 and a C(8) homologue of CP 47,497 were identified as major active ingredients. Due to their reported cannabis-like effects, many European countries have banned these substances. The World Anti-Doping Agency has also explicitly prohibited synthetic cannabinoids in elite sport in-competition. Since urine specimens have been the preferred doping control samples, the elucidation of the metabolic pathways of these substances is of particular importance to implement them in sports drug testing programmes. In a recent report, an in vitro phase-I metabolism study of JWH-018 was presented yielding mainly hydroxylated and N-dealkylatedmetabolites. Due to these findings, a urine sample of a healthy man declaring to have smoked a 'spice' product was screened for potential phase-I and -II metabolites by high-resolution/high-accuracy mass spectrometry in the present report. The majority of the phase-I metabolites observed in earlier in vitro studies of JWH-018 were detected in this urine specimen and furthermore most of their respective monoglucuronides. As no intact JWH-018 was detectable, the monohydroxylated metabolite being the most abundant one was chosen as a target analyte for sports drug testing purposes; a detection method was subsequently developed and validated in accordance to conventional screening protocols based on enzymatic hydrolysis, liquid-liquid extraction, and liquid chromatography/electrospray tandem mass spectrometry analysis. The method was applied to approximately 7500 urine doping control samples yielding two JWH-018 findings and demonstrated its capability for a sensitive and selective identification of JWH-018 and its metabolites in human urine. Copyright (C) 2010 John Wiley & Sons, Ltd.