Novel Synthetic Opioids (NSO) are frequently found in postmortem (PM) and human performance (HP) forensic toxicology casework, resulting in impairment and fatal overdoses. Developing a broad NSO method benefits public health, as it can be used to identify trends in potent opioid use to develop risk management programs. This project aimed to design a comprehensive, rapid and routine method for the selective analysis of over 250 novel synthetic opioids in blood and urine. This method rapidly extracted 150 µL of blood or urine via protein precipitation followed by size-exclusion filtration, evaporation and reconstitution. Separation and data acquisition were achieved on a 12 min LC–MS-MS method using an F5 column. Data processing was expedited with a custom built-in query created in-house that automated processing and enhanced quality assurance. Validation according to ASB/ANSI Standard 036 was performed and applicability of the method was assessed using proficiency test and authentic casework samples. Assessed in blood and urine qualitatively were 261 unique analytes including fentanyl analogs (fentalogs), nitazenes and other miscellaneous synthetic opioids. As 59 isomeric target analytes were placed into groups due to co-elution, there were 202 distinct acquired targets or target - groups. To demonstrate applicability, 27 proficiency test blood samples received over an approximate 4-year period were analyzed with 126 expected results assessed comprising 25 unique target analytes. Additionally, 617 fatal accidental overdoses within San Francisco in 2022 were retroactively analyzed by this method with almost 10% of cases containing a new NSO substance(s). Such trends and NSO substances were previously unknown in this community.

中文翻译：

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通过 LC-MS-MS 分析血液和尿液中的 250 多种新型合成阿片类药物和甲苯噻嗪

新型合成阿片类药物 (NSO) 经常出现在尸检 (PM) 和人类行为 (HP) 法医毒理学案例中，导致药物过量导致损伤和致命。开发广泛的 NSO 方法有利于公众健康，因为它可用于确定强效阿片类药物使用的趋势，以制定风险管理计划。该项目旨在设计一种全面、快速、常规的方法，用于选择性分析血液和尿液中 250 多种新型合成阿片类药物。该方法通过蛋白质沉淀，然后进行尺寸排阻过滤、蒸发和重构，快速提取 150 µL 血液或尿液。使用 F5 色谱柱通过 12 分钟 LC-MS-MS 方法实现分离和数据采集。通过内部创建的自定义内置查询加快了数据处理速度，该查询可实现自动化处理并增强质量保证。根据 ASB/ANSI 标准 036 进行验证，并使用能力验证和真实案例样本评估该方法的适用性。对血液和尿液中的 261 种独特分析物进行了定性评估，其中包括芬太尼类似物（芬他类似物）、硝氮烯和其他各种合成阿片类药物。由于共洗脱，59 种异构体目标分析物被分组，因此有 202 个不同的获得目标或目标组。为了证明适用性，对大约 4 年期间收到的 27 个能力验证血液样本进行了分析，评估了 126 个预期结果，其中包括 25 种独特的目标分析物。此外，通过这种方法对 2022 年旧金山发生的 617 起致命意外用药过量事件进行了追溯分析，其中近 10% 的案例含有新的 NSO 物质。这种趋势和 NSO 物质以前在这个社区中是未知的。