Krotulski Alex J, Mohr Amanda L A, Papsun Donna M, Logan Barry K
Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, 2300 Stratford Ave, Willow Grove, PA, USA.
NMS Labs, 3701 Welsh Rd, Willow Grove, PA, USA.
J Anal Toxicol. 2018 Sep 1;42(7):437-445. doi: 10.1093/jat/bky022.
The number of emerging novel stimulants modified based on beta-keto variations of amphetamine-like substances continues to rise. Dibutylone reports described in the medical and toxicological literature are limited, therefore little information is available in terms of quantitative confirmation or metabolism. During this study, authentic human specimens, including blood, urine, vitreous humor, oral fluid and liver were quantitatively and qualitatively analyzed for the presence of dibutylone and butylone, with paired case history and demographic information. Dibutylone concentrations were variable across all specimen types, specifically ranging from 10 to 1,400 ng/mL in postmortem blood specimens. The metabolic profile of dibutylone was mapped by in vitro incubation with human liver microsomes (HLM). Samples were analyzed using a SCIEX TripleTOF® 5600+ quadrupole time-of-flight mass spectrometer. Data processing was conducted using MetabolitePilot™. Authentic human specimens, including blood, urine, vitreous humor, oral fluid and liver, were utilized for in vivo verification of five HLM-generated metabolites in analytically confirmed cases of dibutylone use. Butylone was confirmed as a metabolite of dibutylone, but issues involving co-ingestion of these two novel stimulants or potential co-existence from synthesis lead to ineffectiveness as a true biomarker. Hydrogenation of the beta-ketone of dibutylone resulted in the most prominent metabolite found in human specimens, and its uniqueness to dibutylone over other stimulants leads to its classification as an appropriate biomarker for dibutylone ingestion. This is the first study to map the metabolic profile of dibutylone, including verification in authentic specimens, confirming metabolic conversion to butylone and identifying biomarkers more useful in forensic toxicological drug testing.
基于苯丙胺类物质的β-酮变体修饰的新型兴奋剂数量持续上升。医学和毒理学文献中关于二丁酮的报道有限,因此在定量确认或代谢方面几乎没有可用信息。在本研究中,对包括血液、尿液、玻璃体液、口腔液和肝脏在内的真实人体标本进行了定量和定性分析,以检测二丁酮和丁酮的存在,并收集了配对的病史和人口统计学信息。所有标本类型中二丁酮的浓度各不相同,特别是在死后血液标本中,浓度范围为10至1400 ng/mL。通过与人肝微粒体(HLM)进行体外孵育来绘制二丁酮的代谢图谱。使用SCIEX TripleTOF® 5600+四极杆飞行时间质谱仪对样品进行分析。使用MetabolitePilot™进行数据处理。在经分析确认使用二丁酮的病例中,利用包括血液、尿液、玻璃体液、口腔液和肝脏在内的真实人体标本对HLM产生的五种代谢物进行体内验证。丁酮被确认为二丁酮的代谢物,但这两种新型兴奋剂共同摄入或合成过程中可能共存的问题导致其作为真正生物标志物的有效性不足。二丁酮β-酮的氢化反应产生了在人体标本中发现的最突出代谢物,其相对于其他兴奋剂对二丁酮的独特性使其被归类为二丁酮摄入的合适生物标志物。这是第一项绘制二丁酮代谢图谱的研究,包括在真实标本中的验证,确认代谢转化为丁酮,并鉴定在法医毒理学药物检测中更有用的生物标志物。