One of the many issues of designer drugs of abuse like synthetic cannabinoids (SCs) such as JWH‐018 is that details on their metabolism has yet to be fully elucidated and that multiple metabolites exist. The presence of isomeric compounds poses further challenges in their identification. Our group has previously shown the effectiveness of gas chromatography‐electron ionization‐tandem mass spectrometry (GC‐EI‐MS/MS) in the mass spectrometric differentiation of the positional isomers of the naphthoylindole‐type SC JWH‐081, and speculated that the same approach could be used for the metabolite isomers. Using JWH‐018 as a model SC, the aim of this study was to differentiate the positional isomers of its hydroxyindole metabolites by GC‐MS/MS. Standard compounds of JWH‐018 and its hydroxyindole metabolite positional isomers were first analyzed by GC‐EI‐MS in full scan mode, which was only able to differentiate the 4‐hydroxyindole isomer. Further GC‐MS/MS analysis was performed by selecting m/z 302 as the precursor ion. All four isomers produced characteristic product ions that enabled the differentiation between them. Using these ions, MRM analysis was performed on the urine of JWH‐018 administered mice and determined the hydroxyl positions to be at the 6‐position on the indole ring. GC‐EI‐MS/MS allowed for the regioisomeric differentiation of the hydroxyindole metabolite isomers of JWH‐018. Furthermore, analysis of the fragmentation patterns suggests that the present method has high potential to be extended to hydroxyindole metabolites of other naphthoylindole type SCs in identifying the position of the hydroxyl group on the indole ring. Copyright © 2016 John Wiley & Sons, Ltd.

中文翻译：

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通过GC-MS / MS建立JWH-018羟吲哚代谢物的质谱羟基位置测定方法

诸如JWH-018之类的合成大麻素（SC）等设计师滥用药物的众多问题之一是，其代谢细节尚未完全阐明，并且存在多种代谢产物。异构化合物的存在对它们的鉴定提出了进一步的挑战。我们的研究小组先前已经证明了气相色谱-电子电离串联质谱（GC-EI-MS / MS）在区分萘并吲哚型SC JWH-081的位置异构体的质谱分析中的有效性，并推测相同方法可用于代谢物异构体。使用JWH-018作为模型SC，本研究的目的是通过GC-MS / MS区分其羟基吲哚代谢产物的位置异构体。首先通过GC-EI-MS以全扫描模式分析JWH-018的标准化合物及其羟基吲哚代谢物的位置异构体，该方法只能区分4-羟基吲哚异构体。通过选择进行进一步的GC-MS / MS分析m / z 302作为前体离子。所有四种异构体均产生特征性的产物离子，从而能够区分它们。使用这些离子，对施用JWH-018的小鼠的尿液进行MRM分析，确定羟基位置在吲哚环的6位。GC‐EI‐MS / MS可以区分JWH‐018的羟基吲哚代谢物异构体的区域异构体。此外，对片段化模式的分析表明，本方法在鉴定吲哚环上的羟基位置方面具有扩展到其他萘基吲哚型SC的羟基吲哚代谢物的潜力。版权所有©2016 John Wiley＆Sons，Ltd.