Krotulski Alex J, Papsun Donna M, De Martinis Bruno S, Mohr Amanda L A, Logan Barry K
Center for Forensic Science Research and Education, 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):467-475. doi: 10.1093/jat/bky025.
N-ethyl pentylone (ephylone) has been identified as the most recent novel stimulant to emerge into the arena of evolving novel psychoactive substances (NPS). Due to its novelty, information regarding case reports with associated quantitative confirmations, biotransformation pathways, and identified unique metabolites will assist the scientific community in understanding the implications of the emergence and risks associated with N-ethyl pentylone use. Authentic blood specimens (n = 26) submitted as part of toxicological death investigations or drugged driving casework tested positive for N-ethyl pentylone, and were quantitatively analyzed by liquid chromatography tandem mass spectrometry (LC-MS-MS). N-ethyl pentylone concentrations ranged from 12 to 1,200 ng/mL, with mean (±standard deviation) and median concentrations of 313 (±366) and 125 ng/mL, respectively, excluding one case measured at 50,000 ng/mL. N-ethyl pentylone was often found in combination with other drugs of abuse and NPS, include a variety of novel opioids including fentanyl analogs. Oral fluid specimens (n = 5), collected from recreational drug users at a dance music festival, were quantitatively analyzed using LC-MS-MS. Concentrations ranged from 12.6 to 1,377 ng/mL. Additional analysis was performed to characterize the metabolic profile of N-ethyl pentylone using human liver microsomes (HLM), followed by confirmation of the presence of the proposed metabolites in a subset of the blood specimens and oral fluid specimens. Metabolomic analysis was performed using a liquid chromatograph quadrupole time-of-flight mass spectrometer (LC-QTOF), followed by data processing using MetabolitePilot™ software. In vivo verification of in vitro HLM-generated metabolites resulted in the confirmation of four metabolites. Reduction of the beta-ketone to an alcohol resulted in the most prominent metabolite found in the authentic specimens, and its uniqueness to N-ethyl pentylone leads to this metabolite being an appropriate biomarker to determine N-ethyl pentylone ingestion. This is the first study to report N-ethyl pentylone concentrations and to characterize the metabolic profile of N-ethyl pentylone.
N-乙基戊酮（戊酮）已被确认为最新出现的新型兴奋剂，进入了不断演变的新型精神活性物质（NPS）领域。由于其新颖性，有关伴有定量确认的病例报告、生物转化途径以及已鉴定出的独特代谢物的信息，将有助于科学界了解N-乙基戊酮出现的影响以及与使用该物质相关的风险。作为毒理学死亡调查或酒驾案件工作的一部分提交的真实血液样本（n = 26），经检测N-乙基戊酮呈阳性，并通过液相色谱串联质谱法（LC-MS-MS）进行了定量分析。N-乙基戊酮浓度范围为12至1200 ng/mL，平均（±标准差）浓度和中位数浓度分别为313（±366）和125 ng/mL，不包括一个测得浓度为50000 ng/mL的样本。N-乙基戊酮经常与其他滥用药物和新型精神活性物质一起被发现，包括各种新型阿片类药物，如芬太尼类似物。从一场电子音乐节上的娱乐性吸毒者那里收集的口腔液样本（n = 5），使用LC-MS-MS进行了定量分析。浓度范围为12.6至1377 ng/mL。利用人肝微粒体（HLM）对N-乙基戊酮的代谢谱进行了进一步分析，随后在一部分血液样本和口腔液样本中确认了所提出的代谢物的存在。使用液相色谱四极杆飞行时间质谱仪（LC-QTOF）进行代谢组学分析，随后使用MetabolitePilot™软件进行数据处理。对体外HLM产生的代谢物进行体内验证，结果确认了四种代谢物。β-酮还原为醇产生了真实样本中发现的最主要代谢物，并且其对N-乙基戊酮的独特性使得该代谢物成为确定N-乙基戊酮摄入情况的合适生物标志物。这是第一项报告N-乙基戊酮浓度并描述其代谢谱的研究。
