Analysis of synthetic cannabinoids using high-resolution mass spectrometry and mass defect filtering: implications for nontargeted screening of designer drugs.
Analysis of synthetic cannabinoids using high-resolution mass spectrometry and mass defect filtering: implications for nontargeted screening of designer drugs.
复制标题
使用高分辨率的质谱和质谱滤波来分析合成大麻素，对设计师药物的非目标筛查的影响。
DOI：
10.1021/ac300509h
复制
发表时间：
2012-07-03
影响因子：
7.4
通讯作者：
Thomas BF
中科院分区：
文献类型：
--
作者：
Grabenauer M;Krol WL;Wiley JL;Thomas BF
由于制造商有能力迅速用密切相关的类似物替代违禁物质，新设计药物的检测仍然是一项分析挑战。传统的靶向质谱法依赖于库搜索、已知质量或多反应监测（MRM）转换，因此通常无法检测或鉴定最近发现的或尚未报道的设计药物类似物。在这里，高分辨率质谱与质量缺陷过滤相结合，作为一种非靶向分析的方法，以检测已知的和新的类似物的设计药物。该技术被深入应用于一系列由吲哚衍生的合成大麻素组成的设计师药物，这些合成大麻素与JWH-018密切相关，JWH-018是一种最近在美国受到管制的物质。具有50 mDa窗口的单个质量缺陷过滤器涵盖了该家族中所有当前已发表结构的80%以上。搜索常见碎片离子的前体离子使得能够检测具有落在质量缺陷滤波器参数范围之外的质量缺陷的化合物。在前体离子搜索之前对碎片离子应用质量缺陷过滤器增加了可以检测到的类似物的宽度。该组合方法定义了对相关分子的广谱搜索。
Detection of new designer drugs remains an analytical challenge due to the ability of manufacturers to rapidly substitute closely related analogs for banned substances. Traditional targeted mass spectrometry methods rely on library searches, known masses, or multiple reaction monitoring (MRM) transitions and are therefore often unable to detect or identify recently discovered or yet unreported designer drug analogs. Here, high-resolution mass spectrometry in conjunction with mass defect filtering is presented as a method for non-targeted analysis to detect both known and novel analogs of designer drugs. The technique is applied in depth to a family of designer drugs composed of indole-derived synthetic cannabinoids closely related to JWH-018, a substance recently controlled in the United States. A single mass defect filter with a 50 mDa window encompasses over 80% of all currently published structures in this family. Searching for precursor ions of common fragment ions enables detection of compounds with mass defects that fall outside the range of mass defect filter parameters. Application of a mass defect filter to fragment ions prior to precursor ion searching increases the breadth of analogs that can be detected. The combined approach defines a broad-spectrum search for related molecules.