Metabolic fate, mass spectral fragmentation, detectability, and differentiation in urine of the benzofuran designer drugs 6-APB and 6-MAPB in comparison to their 5-isomers using GC-MS and LC-(HR)-MSn techniques
Metabolic fate, mass spectral fragmentation, detectability, and differentiation in urine of the benzofuran designer drugs 6-APB and 6-MAPB in comparison to their 5-isomers using GC-MS and LC-(HR)-MSn techniques
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使用 GC-MS 和 LC-(HR)-MSn 技术比较苯并呋喃设计药物 6-APB 和 6-MAPB 与其 5-异构体在尿液中的代谢命运、质谱碎片、可检测性和分化
DOI：
10.1007/s00216-015-8552-2
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发表时间：
2015
影响因子：
4.3
通讯作者：
Maurer HH
中科院分区：
文献类型：
--
作者：
Welter J;Brandt SD;Kavanagh P;Meyer MR;Maurer HH
通过改变已知（附表所列）药物的化学结构，所谓的新精神活性物质的数量仍在增加。作为安非他明的类似物，2-氨丙基苯并呋喃被出售。它们被消费是因为它们的欣快和情感作用。在5-（2-氨丙基）苯并呋喃之后，出现6-（2-氨丙基）苯并呋喃异构体。因此，问题出现了代谢的命运，质谱碎片，和尿液中的可检测性是可比的或不同的，以及如何摄入可以区分。本论文以6-（2-氨丙基）苯并呋喃（6-APB）及其N-甲基衍生物6-MAPB（N-甲基-6-（2-氨丙基）苯并呋喃）为研究对象，对上述问题进行了研究。采用GC-MS和/或液相色谱-高分辨率-质谱法（LC-HR-MSn）在大鼠尿液和人肝脏制备物中鉴别了两种药物的代谢产物。除母体药物外，6-APB的主要代谢产物为4-羧甲基-3-羟基苯丙胺，6-MAPB的主要代谢产物为6-APB（N-去甲基代谢产物）和4-羧甲基-3-羟基甲基苯丙胺。参与6-MAPBN-去甲基化的细胞色素P450（CYP）同工酶为CYP 1A 2、CYP 2D 6和CYP 3A 4。使用作者的GC-MS和LC-MS标准尿液筛查方法，以相应的母体药物为主要靶标，可在大鼠尿液中确认摄入常用剂量的6-APB或6-MAPB。此外，6-APB和6-MAPB从其位置异构体5-APB和5-MAPB的尿液中的区分，成功地进行固相萃取和七氟丁酰化后，通过GC-MS通过其保留时间。
The number of so-called new psychoactive substances (NPS) is still increasing by modification of the chemical structure of known (scheduled) drugs. As analogues of amphetamines, 2-aminopropyl-benzofurans were sold. They were consumed because of their euphoric and empathogenic effects. After the 5-(2-aminopropyl)benzofurans, the 6-(2-aminopropyl)benzofuran isomers appeared. Thus, the question arose whether the metabolic fate, the mass spectral fragmentation, and the detectability in urine are comparable or different and how an intake can be differentiated. In the present study, 6-(2-aminopropyl)benzofuran (6-APB) and itsN-methyl derivative 6-MAPB (N-methyl-6-(2-aminopropyl)benzofuran) were investigated to answer these questions. The metabolites of both drugs were identified in rat urine and human liver preparations using GC-MS and/or liquid chromatography-high resolution-mass spectrometry (LC-HR-MSn). Besides the parent drug, the main metabolite of 6-APB was 4-carboxymethyl-3-hydroxy amphetamine and the main metabolites of 6-MAPB were 6-APB (N-demethyl metabolite) and 4-carboxymethyl-3-hydroxy methamphetamine. The cytochrome P450 (CYP) isoenzymes involved in the 6-MAPBN-demethylation were CYP1A2, CYP2D6, and CYP3A4. An intake of a common users’ dose of 6-APB or 6-MAPB could be confirmed in rat urine using the authors’ GC-MS and the LC-MSnstandard urine screening approaches with the corresponding parent drugs as major target allowing their differentiation. Furthermore, a differentiation of 6-APB and 6-MAPB in urine from their positional isomers 5-APB and 5-MAPB was successfully performed after solid phase extraction and heptafluorobutyrylation by GC-MS via their retention times.
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药物、毒物、农药、污染物及其代谢物的质谱和GC数据（第1、2、3部分）
影响因子：
5.8
作者：
R. Clement
通讯作者：
R. Clement
影响因子：
4.3
作者：
Ewald, Andreas H.;Ehlers, Dorothea;Maurer, Hans H.
通讯作者：
Maurer, Hans H.
影响因子：
4.3
作者：
Welter, Jessica;Kavanagh, Pierce;Maurer, Hans H.
通讯作者：
Maurer, Hans H.
影响因子：
2.3
作者：
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通讯作者：
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网上购买产品中（2-氨基丙基）苯并呋喃（APB）苯环位置异构体的鉴定。
影响因子：
2.9
作者：
A. Stańczuk;N. Morris;E. A. Gardner;P. Kavanagh
通讯作者：
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