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LC-MS-MS 分析非法阿片类药物 U-48800 及相关化合物和涉及 U-48800 的致命案例系列

Analysis of the Illicit Opioid U-48800 and Related Compounds by LC-MS-MS and Case Series of Fatalities Involving U-48800.

机构信息

Department of Toxicology, The Center for Forensic Science Research and Education (CFSRE), 2300 Stratford Ave, Willow Grove, PA 19090, USA.

Department of Toxicology, NMS Labs, 200 Welsh Rd, Horsham, PA 19044, USA.

出版信息

J Anal Toxicol. 2022 Feb 14;46(1):17-24. doi: 10.1093/jat/bkaa180.

DOI:10.1093/jat/bkaa180
PMID:33237987
Abstract

We report a method for the detection and quantitation of 12 drugs and 2 metabolites in the same structural class as the illicit mu-opioid agonist U-47700 in human whole blood. These substances are either known or suspected to be present as potential novel opioids in illicit drug markets. The general class of these drugs was developed in pharmaceutical research programs in the 1970s, but these drugs have recently become of concern for overdoses and death in opioid users in the USA and internationally. The scope of analysis included the following compounds: methylenedioxy U-47700, ethylenedioxy U-47700, ethylenedioxy U-51754, U-69593, U-47931E (bromadoline), U-47700, U-48800, U-49900, U-51754, U-50488, propyl U-47700 and isopropyl U-47700. Additionally, two metabolites N,N-didesmethyl U-47700 and desmethyl U-47700 were also included in the scope. Drugs were extracted from human whole blood using solid-phase extraction, and the extracts were analyzed by liquid chromatography--tandem mass spectrometry. The assay was validated with respect to bias, carryover, interference, within-run and between-run precision, and accuracy. Eight medicolegal death investigation cases that had screened positive for U-48800 by liquid chromatography--time-of-flight mass spectrometry were successfully confirmed and quantified using this method. The mean and median concentrations of U-48800 in these cases were 2.5 (±2.1) and 1.8 ng/mL, respectively, with a range of concentrations of 0.27-6.2 ng/mL. Case history information including the presence of other drugs in combination are described and discussed.

摘要

我们报告了一种在人全血中同时检测和定量 12 种药物和 2 种代谢物的方法,这些药物与非法 μ-阿片激动剂 U-47700 属于同一结构类别。这些物质要么是已知的,要么是怀疑存在于非法药物市场中的潜在新型阿片类药物。这些药物的一般类别是在 20 世纪 70 年代的药物研究计划中开发的,但最近在美国和国际上,这些药物因阿片类药物使用者过量和死亡而受到关注。分析范围包括以下化合物:亚甲二氧基 U-47700、乙撑二氧基 U-47700、乙撑二氧基 U-51754、U-69593、U-47700、U-48800、U-49900、U-51754、U-50488、丙基 U-47700 和异丙基 U-47700。此外,还包括两种代谢物 N,N-二去甲基 U-47700 和去甲基 U-47700。药物用人全血中的固相萃取提取,提取液用液相色谱-串联质谱分析。该测定方法在偏倚、交叉污染、干扰、批内和批间精密度以及准确度方面进行了验证。通过液相色谱-飞行时间质谱筛查出 U-48800 呈阳性的 8 例法医学死亡调查案例,成功地使用该方法进行了确认和定量。这些案例中 U-48800 的平均浓度和中位数浓度分别为 2.5(±2.1)和 1.8ng/mL,浓度范围为 0.27-6.2ng/mL。描述并讨论了包括其他药物组合存在的案例病史信息。

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