Office of the Chief Medical Examiner, 1 Newhall Street, San Francisco, CA, United States.
Laboratory Medicine, University of California, San Francisco, San Fransisco, CA, United States.
J Anal Toxicol. 2024 Mar 28;48(3):150-164. doi: 10.1093/jat/bkae009.
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.
新型合成阿片类药物（NSO）经常在死后（PM）和人体表现（HP）法医毒理学案例中被发现，导致功能障碍和致命的过量用药。开发广泛的 NSO 方法有益于公共健康，因为它可以用于识别强效阿片类药物使用趋势，以制定风险管理计划。本项目旨在设计一种全面、快速和常规的方法，用于选择性分析血液和尿液中的 250 多种新型合成阿片类药物。该方法通过蛋白质沉淀快速提取 150μL 的血液或尿液，然后进行尺寸排阻过滤、蒸发和再构成。使用 F5 柱在 12 分钟的 LC-MS-MS 方法上进行分离和数据采集。使用内部创建的自定义内置查询加速数据处理，该查询自动化处理并增强了质量保证。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方法的适用性。在血液和尿液中定性评估了 261 种独特的分析物，包括芬太尼类似物（fentalogs）、硝西泮和其他杂项合成阿片类药物。由于 59 种同系物目标分析物由于共洗脱而被分为一组，因此有 202 种不同的获得的目标或目标组。为了证明适用性，在大约 4 年的时间内分析了 27 个收到的能力验证血液样本，评估了 126 个预期结果，其中包含 25 种独特的目标分析物。此外，通过该方法对 2022 年旧金山的 617 例致命意外过量用药进行了回顾性分析，其中近 10%的病例含有新的 NSO 物质。在该社区中，此前从未发现过此类趋势和 NSO 物质。
