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Concentrations of para-Fluorofuranylfentanyl (FFF) in Paired Central and Peripheral Blood Collected During Postmortem Death Investigations.
Journal of Analytical Toxicology ( IF 2.5 ) Pub Date : 2021-03-10 , DOI: 10.1093/jat/bkab025
Judith Rodriguez Salas 1 , Alex J Krotulski 1 , Reta Newman 2 , Jon R Thogmartin 3 , Amanda L A Mohr 1 , Barry K Logan 1, 4
Affiliation  

The opioid epidemic in the United States (U.S.) has been associated with an increasing mortality rate in large part due to the emergence and proliferation of synthetic opioids over the last fifteen years. Fentanyl and its analogues have played a large part in these statistics due to their potency and toxicity. Fluorofuranylfentanyl (FFF) is a fentanyl analogue that emerged in the U.S. in 2018 and was associated with numerous adverse events and deaths. During this study, a liquid chromatography tandem mass spectrometry (LC-MS/MS) 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 (LC-QTOF-MS). 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). Comparison of central to peripheral blood concentrations were evaluated to determine the possibility of postmortem redistribution (PMR). The metabolism of ortho-FFF was studied and found to undergo metabolic processes similar to fentanyl, producing ortho-fluorofuranyl-norfentanyl, fluoro-4-ANPP, 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 analogues, as they pose significant risks to public health and public safety.

中文翻译:

死后死亡调查期间收集的成对的中央和外周血中对氟呋喃基芬太尼(FFF)的浓度。

在美国(美国),阿片类药物的流行与死亡率的上升有关,这在很大程度上是由于过去十五年来合成阿片类药物的出现和扩散所致。芬太尼及其类似物由于其效力和毒性而在这些统计数据中起了很大的作用。氟呋喃基芬太尼(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(LC-MS / MS)工作流程,以准确鉴定佛罗里达州Pinellas County的法医学死亡调查病例中存在的FFF异构体(邻位,间位和对位)。 。在尸检时采集的中央和外周血样本中对FFF进行定​​量。此外,使用液相色谱四极杆飞行时间质谱(LC-QTOF-MS)研究了FFF的代谢。在29个死后病例中对FFF进行了定量确认;未检测到FFF的其他异构体。中枢血药浓度范围为0.66至73 ng / mL(平均值= 11±14 ng / mL,中位数= 10 ng / mL),外周血浓度范围为0.53至23 ng / mL(平均值为5.7±6.4 ng / mL,中位数= 2.7 ng / mL)。评价中心血液与外周血浓度的比较,以确定死后再分布(PMR)的可能性。研究了邻FFF的代谢,发现代谢过程类似于芬太尼,产生了邻氟呋喃基-去甲芬太尼,氟-4-ANPP和羟基化物种。这项研究的结果证明了FFF的毒性及其在法医死亡研究中的意义。实验室必须对新的或重新出现的芬太尼类似物保持警觉,因为它们对公共卫生和公共安全构成重大风险。
更新日期:2021-03-10
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