Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, New Jersey 08544, United States.
Anal Chem. 2023 Nov 28;95(47):17300-17310. doi: 10.1021/acs.analchem.3c03451. Epub 2023 Nov 15.
Over the last two decades, hundreds of new psychoactive substances (NPSs), also known as "designer drugs", have emerged on the illicit drug market. The toxic and potentially fatal effects of these compounds oblige laboratories around the world to screen for NPS in seized materials and biological samples, commonly using high-resolution mass spectrometry. However, unambiguous identification of a NPS by mass spectrometry requires comparison to data from analytical reference materials, acquired on the same instrument. The sheer number of NPSs that are available on the illicit market, and the pace at which new compounds are introduced, means that forensic laboratories must make difficult decisions about which reference materials to acquire. Here, we asked whether retrospective suspect screening of population-scale mass spectrometry data could provide a data-driven platform to prioritize emerging NPSs for assay development. We curated a suspect database of precursor and diagnostic fragment ion masses for 83 emerging NPSs and used this database to retrospectively screen mass spectrometry data from 12,727 urine drug screens from one Canadian province. We developed integrative computational strategies to prioritize the most reliable identifications and tracked the frequency of these identifications over a 3 year study period between August 2019 and August 2022. The resulting data were used to guide the acquisition of new reference materials, which were in turn used to validate a subset of the retrospective identifications. Last, we took advantage of matching clinical reports for all 12,727 samples to systematically benchmark the accuracy of our retrospective data analysis approach. Our work opens up new avenues to enable the rapid detection of emerging illicit drugs through large-scale reanalysis of mass spectrometry data.
在过去的二十年中，数以百计的新型精神活性物质（NPSs），也被称为“设计毒品”，已经出现在非法毒品市场上。这些化合物的毒性和潜在致命作用迫使世界各地的实验室对缴获的材料和生物样本中的 NPS 进行筛选，通常使用高分辨率质谱法。然而，通过质谱法对 NPS 进行明确识别需要与在同一仪器上获得的分析参考物质的数据进行比较。市场上可用的 NPS 数量之多，以及新化合物不断推出的速度，意味着法医实验室必须就购买哪些参考物质做出艰难的决定。在这里，我们想知道对人群规模的质谱数据进行回溯性可疑筛选是否可以提供一个数据驱动的平台，以便优先对新兴 NPS 进行检测方法的开发。我们创建了一个包含 83 种新兴 NPS 的前体和诊断碎片离子质量的可疑数据库，并使用该数据库对来自加拿大一个省的 12727 份尿液药物筛选的质谱数据进行回溯性筛选。我们开发了综合计算策略来优先考虑最可靠的鉴定，并在 2019 年 8 月至 2022 年 8 月的 3 年研究期间跟踪这些鉴定的频率。由此产生的数据用于指导新参考物质的获取，这些物质反过来又被用于验证回溯性鉴定的一部分。最后，我们利用所有 12727 个样本的匹配临床报告，系统地对我们的回溯数据分析方法的准确性进行基准测试。我们的工作为通过对大规模质谱数据进行重新分析来快速检测新兴非法药物开辟了新途径。
