识别新的精神活性物质的综合方法

识别新的精神活性物质的综合方法

对于毒品执法机构来说，新的精神活性物质（NP）或设计师药物的出现是一个持续的问题。这些药物旨在模仿受控物质的作用，但具有稍微修改的新型化学结构的受控物质立法。在欧洲，2015年向欧盟（EU）监测机构报告了100种此类药物，上一年增加了25％。在2013年，大约有35,000人癫痫发作。从那以后，全球新事件的比率在每年50至100之间变化。这些物质的合法性可能会给消费者带来错误的印象，即他们比受控药物更安全。但是，实际上，它们比他们试图模仿包括剧烈副作用的物质更具毒性。

A challenge for enforcement is that, by their very nature, these substances have not been characterized, meaning a lack of reference standards to facilitate their detection. In the EU, customs authorities play a critical role in detecting NPS as they arrive into Europe. But most customs laboratories do not have access to advanced analytical tools such as nuclear magnetic resonance (NMR) or high-resolution tandem mass-spectrometry (HR-MS/MS).

在欧盟，欧洲委员会的联合研究中心负责确定海关抓住的未知物质。联合研究中心建立了一个研究项目，以帮助推进NP的快速识别。作为其中的一部分，他们进行了一项研究，以描述从中国送来的两种药物，这些药物在欧洲海关向买方途中抓住。买家打算购买合成大麻素的5F-AMB和设计师Benzodiazepine的Clonazolam。这些药物类型通常用于增强一种药物的高度或减少其不良反应。该团队探讨了如何使用来自不同技术和仪器的信息来实现新的未知物质的完整分析确认。

一系列分析
Customs laboratories can perform routine substance analysis with gas chromatography mass spectrometry (GC-MS) or Fourier Transform infrared (FTIR) spectroscopy. These techniques can indicate the chemical structure of an unknown substance, but not a full identification. They can be sufficient if the substance is previously known or by spectral library search and match. For the two samples in this study, GC-MS and FTIR for the first sample showed a close match with existing analytical data for 5F-AMB. The second sample did not match existing data but showed some similarity to existing spectra for an indazole-based synthetic cannabinoid called AB-CHMINACA.

The researchers obtained NMR spectra for the two samples at 300 K on a Bruker Avance III HD 600 spectrometer equipped with a 5 mm QCI cryoprobe, allowing for structural elucidation.
They then performed HR-MS/MS to obtain an accurate mass spectrum and precise determination of the monoisotopic mass. This data was in agreement with the NMR spectroscopic data. The NMR data also facilitated fragmentation matching because the theoretical structure of the molecule was known.
The team also performed Raman spectroscopy on the drug samples. This data, when combined with the NMR data, allowed them to confirm their proposed structure for the two substances.

A Dangerous Combination
Integrating the information obtained from the series of analyses, the researchers identified the substances as 5F-AMB and another synthetic cannabinoid APP-CHMINACA, also known as PX-3. The buyer intended to purchase one synthetic cannabinoid and one benzodiazepine, presumably for their synergistic effects. But the findings show they would instead have received two synthetic cannabinoids. These substances act similarly to cannabis but with greater toxicity and, if consumed together, could have led to severe intoxication. The authors say that the results highlight the hazard posed to consumers by NPS.

研究人员注意到,尽管gc - ms和FTIR can provide a lot of information about NPS, additional techniques are needed to carry out full analytical confirmation. GC-MS and FTIR are suitable for routine control as they are quick and cost-efficient. They can be sufficient to confirm the structure of a substance if it matches existing data. However, the researchers say that low-resolution MS instruments, like those typically used in routine control, will not be able to confirm the chemical structure of a new unknown substance. While confirming the structure of NPS remains challenging, they say their approach, with a complete integrated analytical strategy, permits the rapid and complete characterization of an unknown substance.

创新构建
在这项研究中，研究人员使用了Bruker Avance NMR光谱仪。该系列的最新版本是Avance Neo，它建立在给每一代的创新基础上。Avance Neo提供了增强的数字控制，改进的动态范围以及更大的灵活性和可扩展性。一项主要功能是其“接触”技术，其中每个NMR渠道既充当发射器又是接收器。这使每个通道都可以作为独立的光谱仪操作，从而轻松促进多接收实验。Avance NEO包括一个易用使用和系统功率控制的配电单元，这是一家嵌入式采集服务器，并配备了Bruker的行业标准Topspin软件。

End-to-end Solutions of Forensic Drug Testing
布鲁克（Bruker）提供了当今执法部门法医药物分析中全球使用的最广泛的分析技术。该投资组合包括台式和落地NMR，FTIR和拉曼光谱和质谱法等光学方法。这使布鲁克成为唯一的端到端解决方案提供商，从癫痫发作的位置进行了标记，将应用程序标记为麻醉品识别和量化的每个阶段，而癫痫发作的位置是对高绩效法医实验室中新的和未知物质的全面分析的关键。。我们使客户能够通过各种正交技术生成一致的法律程序分析数据。

Reference
Vicente JL, Chassaigne H, Holland MV et al. Systematic analytical characterization of new psychoactive substances: A case study. Forensic Science International 2016; 265:107-115.