The opioid epidemic in the USA has been associated with an increasing mortality rate in large part due to the emergence and proliferation of synthetic opioids over the last 15 years. Fentanyl and its analogs have played a large part in these statistics due to their potency and toxicity. Fluorofuranylfentanyl (FFF) is a fentanyl analog that emerged in the USA in 2018 and was associated with numerous adverse events and deaths. During this study, a liquid chromatography tandem mass spectrometry workflow was developed to accurately identify the isomer of FFF present (ortho- vs. meta- vs. para-) in medicolegal death investigation cases from Pinellas County, Florida. FFF was quantified in central and peripheral blood samples collected at autopsy. In addition, the metabolism of FFF was studied using liquid chromatography quadrupole time-of-flight mass spectrometry. para-FFF was quantitatively confirmed in 29 postmortem cases; no other isomer of FFF was detected. Central blood concentrations ranged between 0.66 and 73 ng/mL (mean = 11 ± 14 ng/mL, median = 10 ng/mL) and peripheral blood concentrations ranged between 0.53 and 23 ng/mL (mean = 5.7 ± 6.4 ng/mL, median = 2.7 ng/mL). A comparison of central to peripheral blood concentrations was evaluated to determine the possibility of postmortem redistribution. The metabolism of ortho-FFF was studied and found to undergo metabolic processes similar to fentanyl, producing ortho-fluorofuranyl-norfentanyl, fluoro-4-anilino-N-phenethylpiperidine, and hydroxylated species. The results of this study demonstrate the toxicity of FFF and its implication in medicolegal death investigations. Laboratories must remain aware of new or re-emerging fentanyl analogs, as they pose significant risks to public health and public safety.

中文翻译：

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死后死亡调查期间收集的配对中央和外周血中对氟呋喃芬太尼的浓度

美国阿片类药物的流行与死亡率的增加有关，这在很大程度上是由于过去 15 年合成阿片类药物的出现和扩散。由于其效力和毒性，芬太尼及其类似物在这些统计数据中发挥了重要作用。氟呋喃芬太尼 (FFF) 是一种芬太尼类似物，于 2018 年在美国出现，与许多不良事件和死亡有关。在这项研究中，开发了液相色谱串联质谱工作流程，以准确识别佛罗里达州皮内拉斯县法医死亡调查案例中存在的 FFF 异构体（邻位与间位与对位）。FFF 在尸检时收集的中央和外周血样本中进行量化。此外，使用液相色谱四极杆飞行时间质谱法研究了 FFF 的代谢。在 29 例死后病例中定量确认了 para-FFF；未检测到其他 FFF 异构体。中心血浓度范围在 0.66 和 73 ng/mL 之间（平均值 = 11 ± 14 ng/mL，中值 = 10 ng/mL），外周血浓度范围在 0.53 和 23 ng/mL 之间（平均值 = 5.7 ± 6.4 ng/mL，中位数 = 2.7 ng/mL)。评估中心血浓度与外周血浓度的比较以确定死后重新分布的可能性。研究了邻-FFF 的代谢，发现其代谢过程类似于芬太尼，产生邻-氟呋喃-去甲芬太尼、氟-4-苯胺基-N-苯乙基哌啶和羟基化物质。这项研究的结果证明了 FFF 的毒性及其在法医死亡调查中的意义。实验室必须保持对新的或重新出现的芬太尼类似物的认识，因为它们对公共健康和公共安全构成重大风险。