Dimethocaine, a synthetic cocaine analogue: studies on its in-vivo metabolism and its detectability in urine by means of a rat model and liquid chromatography–linear ion-trap (high-resolution) mass spectrometry

Dimethocaine, a synthetic cocaine analogue: studies on its in-vivo metabolism and its detectability in urine by means of a rat model and liquid chromatography–linear ion-trap (high-resolution) mass spectrometry
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聚美多卡因,一种合成可卡因类似物:通过大鼠模型和液相色谱-线性离子阱(高分辨率)质谱法研究其体内代谢及其在尿液中的可检测性

DOI:
10.1007/s00216-013-7539-0
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发表时间:
2014
影响因子:
4.3
通讯作者:
Maurer HH
Maurer HH
中科院分区:
化学2区
文献类型:
--
作者:
Meyer MR;Lindauer C;Welter J;Maurer HH

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二甲卡因(DMC,larocaine)是可卡因的一种合成衍生物,是一种广泛分布的“法律的高”,作为“新精神活性物质”(NEP)消费,没有任何安全性测试,例如代谢研究。因此,本工作的目的是通过使用液相色谱-(高分辨率)质谱(LC-HRMSn)研究其在体内和体外代谢。将DMC给予雄性Wistar大鼠(20 mg kg-1),并在酶促裂解结合物后通过固相萃取或通过使用蛋白沉淀(PP)提取其尿液。通过LC-HRMSn分离和鉴定代谢产物。主要的阶段I反应是酯水解、脱乙基化、芳族体系的羟基化以及这些反应的组合。主要的第二阶段反应是未改变的母体化合物和几种第一阶段代谢物的对氨基苯甲酸部分的N-乙酰化。然后将鉴别的代谢物用于鉴别普通用户剂量给药后大鼠尿液中的DMC。采用GC-MS和LC-MS标准尿液筛查方法(SUSAs),可检测出DMC及其代谢产物。
Dimethocaine (DMC, larocaine), a synthetic derivative of cocaine, is a widely distributed “legal high” consumed as a “new psychoactive substance” (NPS) without any safety testing, for example studies of metabolism. Therefore, the purpose of this work was to study its in-vivo and in-vitro metabolism by use of liquid chromatography–(high resolution) mass spectrometry (LC–HRMSn). DMC was administered to male Wistar rats (20 mg kg−1) and their urine was extracted either by solid-phase extraction after enzymatic cleavage of conjugates or by use of protein precipitation (PP). The metabolites were separated and identified by LC–HRMSn. The main phase I reactions were ester hydrolysis, deethylation, hydroxylation of the aromatic system, and a combination of these. The main phase II reaction wasN-acetylation of thep-aminobenzoic acid part of the unchanged parent compound and of several phase I metabolites. The metabolites identified were then used for identification of DMC in rat urine after application of a common user’s dose. By use of GC–MS and LC–MSnstandard urine-screening approaches (SUSAs), DMC and its metabolites could be detected in the urine samples.
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发表时间: 2008-04-01
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发表时间: 2004
期刊: Drug metabolism and disposition: the biological fate of chemicals
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