Isotonitazene Quantitation and Metabolite Discovery in Authentic Forensic Casework
Isotonitazene Quantitation and Metabolite Discovery in Authentic Forensic Casework
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DOI：
10.1093/jat/bkaa016
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发表时间：
2020-07-01
影响因子：
2.5
通讯作者：
Logan, Barry K.
中科院分区：
文献类型：
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作者：
Krotulski, Alex J.;Papsun, Donna M.;Logan, Barry K.
随着非芬太尼相关物质出现在法医毒理学案件中，合成阿片类药物的情况继续发生变化。在最新出现的合成阿片类药物中，异戊二烯是苯并咪唑类镇痛化合物的类似物。异戊二烯是一种活性强效的合成阿片类药物，但这种化合物在吸毒者中引起毒性的程度以前是未知的。本报告描述了通过标准添加以及吸毒者体内代谢谱测定在血液、尿液和玻璃体液中异戊二烯的确认和定量。定量分析采用液相色谱-串联质谱法（LC-MS-MS），代谢物发现采用液相色谱-四极杆飞行时间质谱法（LC-QTOF-MS）。总共有18例确诊异烟肼呈阳性，其中9例以前对任何阿片类药物呈阴性。血液中异烟肼的平均浓度为2.2 +/- 2.1 ng/mL（中位数为1.75 ng/mL，范围为0.4-9.5 ng/mL），尿液中异烟肼的平均浓度为2.4 +/- 1.4 ng/mL（中位数为2.7 ng/mL，范围为0.6-4.0 ng/mL）。2例患者血中异戊二烯最低浓度为0.4 ng/mL，无其他阿片类药物存在；死亡调查结果。在体内检测到异烟肼的四种代谢物。N-和o-脱烷基产物被确定为最突出的尿液生物标志物，而5-氨基异戊二烯在大多数血液样本中被鉴定出来。2020年初，异烟肼在美国的流行和普及程度继续增加。毒理学家、法医和验尸官应了解标准测试范围之外的新型阿片类药物，特别是在法医死亡调查中。法医科学家应该在检测程序中加入异戊二氮，公共卫生官员应该就强效新药和使用阿片类药物的危险进行咨询。
The synthetic opioid landscape continues to change as non-fentanyl-related substances appear in forensic toxicology casework. Among the newest synthetic opioids to emerge is isotonitazene, an analogue of a benzimidazole class of analgesic compounds. Isotonitazene is an active and potent synthetic opioid, but the extent to which this compound is causing toxicity among drug users was previously unknown. This report describes the confirmation and quantitation of isotonitazene in blood, urine and vitreous fluid through standard addition, as well as in vivo metabolic profile determination in drug users. Quantitative analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS-MS), and metabolite discovery was performed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). In total, 18 cases were confirmed positive for isotonitazene, and nine of them were previously negative for any opioid. The average isotonitazene concentration in blood was 2.2 +/- 2.1 ng/mL (median 1.75 ng/mL, range 0.4-9.5 ng/mL), and the average isotonitazene concentration in urine was 2.4 +/- 1.4 ng/mL (median 2.7 ng/mL, range 0.6-4.0 ng/mL). The lowest concentration of isotonitazene in blood was 0.4 ng/mL (two cases) with no other opioids present; findings in death investigations. Four metabolites of isotonitazene were detected in vivo. N- and O-dealkylation products were determined to be the most prominent urinary biomarkers, while 5-amino-isotonitazene was identified in most blood samples. The prevalence and popularity of isotonitazene continue to increase in the United States in early 2020. Toxicologists, medical examiners and coroners should be aware of novel opioids outside the standard scope of testing, especially in medicolegal death investigations. Forensic scientists should add isotonitazene to testing procedures, and public health officials should counsel about potent new drugs and the dangers of opioid use.