A Forward-Thinking Approach to Addressing the New Synthetic Opioid 2-Benzylbenzimidazole Nitazene Analogs by Liquid Chromatography-Tandem Quadrupole Mass Spectrometry (LC-QQQ-MS).
A Forward-Thinking Approach to Addressing the New Synthetic Opioid 2-Benzylbenzimidazole Nitazene Analogs by Liquid Chromatography-Tandem Quadrupole Mass Spectrometry (LC-QQQ-MS).
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DOI：
10.1093/jat/bkab117
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发表时间：
2022-03-21
影响因子：
2.5
通讯作者：
Logan BK
中科院分区：
文献类型：
--
作者：
Walton SE;Krotulski AJ;Logan BK
新型精神活性物质继续对公共健康和安全构成威胁。最新出现的合成阿片类药物2-苄基苯并咪唑类似物（也称为硝氮类）中的新药数量已开始主导目前的新合成阿片类药物（NSO）亚类。我们描述了一种液相色谱-串联四极杆质谱法定量的9个类似物和/或代谢物的药物在这个系列：异托尼他嗪，美托尼他嗪，质子尼他嗪，依托尼他嗪，氯尼他嗪，氟尼他嗪，N-去乙基异托尼他嗪，5-氨基异托尼他嗪和4-羟基尼他嗪在人体全血，尿液和组织。使用碱性液-液萃取制备用于分析的样品。采用C-18分析柱进行色谱分离。采用多反应监测模式进行检测。分析物的校准范围为0.5-50 ng/mL（5-氨基异托噻嗪除外，其为1.0-50 ng/mL）。检测限为0.1 ng/mL，定量限为0.5 ng/mL。该方法无残留或干扰。观察到电离增强，但不影响定量。所有分析物均通过了方法验证评估。怀疑含有NSO的真实人体样本是从法医和验尸官办公室以及合作法医毒理学实验室获得的。在92份血液样本中确认了异托尼嗪，并在各种基质中确认了其代谢产物。同时检出甲硝氮35例，氟硝氮5例，质子硝氮3例，依托硝氮2例，布硝氮1例。这些新出现的2-苄基苯并咪唑类似物通常与苯并二氮杂卓和阿片类药物（例如，氟吡唑仑、芬太尼）。Nitazene类似物是有效的深奥药物，在常规毒理学筛选过程中可能无法识别，需要基于敏感仪器的专门测定来准确表征这些NSO。
Novel psychoactive substances (NPS) continue to represent a threat to public health and safety. The number of new drugs in the latest emergent synthetic opioid class—the 2-benzylbenzimidazole analogs—also called the nitazenes—has begun to dominate the current new synthetic opioid (NSO) subclass of NPS. We describe a liquid chromatography–tandem quadrupole mass spectrometry method for the quantification of nine analogs and/or metabolites of drugs in this series: isotonitazene, metonitazene, protonitazene, etonitazene, clonitazene, flunitazene, N-desethyl isotonitazene, 5-amino isotonitazene and 4ʹ-hydroxy nitazene in human whole blood, urine, and tissue. Samples were prepared for analysis using a basic liquid–liquid extraction. Chromatographic separation was achieved using a C-18 analytical column. Multiple reaction monitoring mode was used for detection. The calibration range for the analytes was 0.5–50 ng/mL (except for 5-amino isotonitazene, which was 1.0–50 ng/mL). The limit of detection was 0.1 ng/mL, and the limit of quantitation was 0.5 ng/mL. The method had no carryover or interferences. Ionization enhancement was observed but did not affect quantitation. All analytes passed the method validation assessment. Authentic human samples suspected of containing NSOs were obtained from a medical examiner and coroner offices, as well as partnering forensic toxicology laboratories. Isotonitazene was confirmed in 92 blood samples, and its metabolites were confirmed across various matrices. Metonitazene (n = 35), flunitazene (n = 5), protonitazene (n = 3), etodesnitazene (n = 2) and butonitazene (n = 1) were also detected in cases. These newly emerging 2-benzylbenzimidazole analogs were commonly found in combination with NPS benzodiazepines and opioids (e.g., flualprazolam, fentanyl). Nitazene analogs are potent esoteric drugs that may not be identified during routine toxicological screening, and specialized assays based on sensitive instrumentation are needed to accurately characterize these NSOs.
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影响因子：
2.9
作者：
Krotulski, Alex J.;Papsun, Donna M.;Logan, Barry K.
通讯作者：
Logan, Barry K.
影响因子：
2.9
作者：
Blanckaert, Peter;Cannaert, Annelies;Stove, Christophe
通讯作者：
Stove, Christophe
影响因子：
1.6
作者：
Krotulski, Alex J.;Papsun, Donna M.;Logan, Barry K.
通讯作者：
Logan, Barry K.
影响因子：
5
作者：
Vandeputte, Marthe M.;Van Uytfanghe, Katleen;Stove, Christophe P.
通讯作者：
Stove, Christophe P.
影响因子：
2.5
作者：
Papsun, Donna M.;Krotulski, Alex J.;Logan, Barry K.
通讯作者：
Logan, Barry K.