Brorphine-Investigation and quantitation of a new potent synthetic opioid in forensic toxicology casework using liquid chromatography-mass spectrometry
Brorphine-Investigation and quantitation of a new potent synthetic opioid in forensic toxicology casework using liquid chromatography-mass spectrometry
复制标题
DOI：
10.1111/1556-4029.14623
复制
发表时间：
2020-11-17
影响因子：
1.6
通讯作者：
Logan, Barry K.
中科院分区：
文献类型：
--
作者：
Krotulski, Alex J.;Papsun, Donna M.;Logan, Barry K.
新的合成阿片类药物继续作为新型精神活性物质出现在非法药物市场上。异烟肼于2019年年中出现，在几个月内成为美国最普遍的NPS阿片类药物。美国缉毒局（Drug Enforcement Administration）通知其打算在2020年中期将异戊二烯列入清单，这导致其受欢迎程度下降，并被一种新的NPS阿片类药物：吗啡所取代。啡是一种强效的合成阿片类药物，但以前很少有关于其毒性或与损伤和死亡有关的信息。本实验室开发了一种标准添加法鉴定和定量确认啡的方法。采用液相色谱-串联质谱法（LC-MS/MS）进行定量分析。体外和体内代谢研究分别使用混合的人肝微粒体和真实的生物标本，并使用液相色谱四极杆飞行时间质谱（LC-QTOF-MS）进行分析。在20个真实的法医案件中确认了吗啡，通常与芬太尼（100%）和氟拉唑仑（80%）合用。血中啡平均浓度为2.5 +/- 3.1 ng/mL（中位数：1.1 ng/mL，范围：0.1-10 ng/mL）。尿中啡的平均浓度为4.6±7.6 ng/mL（中位数：1.6 ng/mL，范围：0.2 ~ 23 ng/mL）。大多数病例来自中西部各州。代谢被证实包括n -脱烷基和羟基化。详细的病例历史和尸检结果提出在此。在美国，吗啡的使用率持续上升。法医科学家应该继续意识到新的阿片类药物的不断出现，特别是那些超出毒理学测试标准范围的阿片类药物。
New synthetic opioids continue to appear as novel psychoactive substances (NPS) on illicit drug markets. Isotonitazene emerged in mid-2019, becoming the most prevalent NPS opioid in the United States within a few months. Notification by the Drug Enforcement Administration of its intent to schedule isotonitazene in mid-2020 led to its decline in popularity and replacement with a new NPS opioid: brorphine. Brorphine is a potent synthetic opioid, but little information was previously available regarding its toxicity or involvement in impairment and death. Our laboratory developed an assay for the identification and quantitative confirmation of brorphine using standard addition. Quantitative analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In vitro and in vivo metabolism studies were performed using pooled human liver microsomes and authentic biological specimens, respectively, with analysis by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Brorphine was confirmed in 20 authentic forensic cases, commonly found in combination with fentanyl (100%) and flualprazolam (80%). The average concentration of brorphine in blood was 2.5 +/- 3.1 ng/mL (median: 1.1 ng/mL, range: 0.1-10 ng/mL). The average concentration of brorphine in urine was 4.6 +/- 7.6 ng/mL (median: 1.6 ng/mL, range: 0.2-23 ng/mL). The majority of cases originated from Midwestern states. Metabolism was verified to included N-dealkylation and hydroxylation. Detailed case histories and autopsy findings are presented herein. The prevalence of brorphine continues to increase in the United States. Forensic scientists should remain aware of the ongoing emergence of new opioids, especially those outside a standard scope of toxicology testing.