Analysis of Fentanyl and 18 Novel Fentanyl Analogs and Metabolites by LC-MS-MS, and report of Fatalities Associated with Methoxyacetylfentanyl and Cyclopropylfentanyl
Analysis of Fentanyl and 18 Novel Fentanyl Analogs and Metabolites by LC-MS-MS, and report of Fatalities Associated with Methoxyacetylfentanyl and Cyclopropylfentanyl
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DOI：
10.1093/jat/bky035
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发表时间：
2018-11-01
影响因子：
2.5
通讯作者：
Logan, Barry K.
中科院分区：
文献类型：
--
作者：
Fogarty, Melissa F.;Papsun, Donna M.;Logan, Barry K.
甲氧基乙酰芬太尼和环丙基芬太尼是两种最新的非法阿片类药物，正在渗透海洛因市场。美国缉毒局（DEA）在2017年第三季度报告中报告称，从DEA实验室系统分析的药物证据中，甲氧基乙酰芬太尼和环丙基芬太尼分别被化学鉴定了7次和5次;第三季度是DEA实验室系统首次鉴定环丙基芬太尼，而甲氧基乙酰芬太尼在2017年第二季度被报告了一次。开发了一种使用液相色谱串联质谱法定量芬太尼、去甲芬太尼和17种芬太尼类似物的方法：呋喃基芬太尼、丁酰芬太尼、去丙酰芬太尼（4-ANPP）、甲氧基乙酰基芬太尼、四氢呋喃芬太尼、氟-异丁酰芬太尼、丙烯酰芬太尼、对氟芬太尼、邻氟芬太尼、卡芬太尼、β-甲基芬太尼、异丁酰芬太尼、对甲基芬太尼、环戊基芬太尼、环丙基芬太尼，β-羟基芬太尼和α-甲基芬太尼。所有化合物的校准范围为0.1-100 ng/mL。来自佛罗里达、伊利诺伊、密歇根和田纳西的42例涉及环丙基芬太尼和甲氧基乙酰芬太尼的尸检病例的血样被提交进行毒理学分析。环丙基芬太尼检测阳性病例（n = 32）的平均和中位浓度分别为15.3（+/- 11.9）ng/mL和12.3 ng/mL，范围为1.4-43.3 ng/mL。定量确认的11例（3例低于定量限）甲氧乙酰芬太尼的平均（+/- SD）和中位浓度分别为17.7（+/- 11.4）ng/mL和15.1 ng/mL，范围为0.21-39.9 ng/mL。这些新的非法物质通常不在医院和毒理学实验室的常规药物检测范围之内，或低于在生物样本中检测这些物质的灵敏度水平。这些化合物以前未在人体中进行过研究;因此，能够将病例报告中的药理学作用与尸检标本中发现的定量值相关联是非常重要的。
Methoxyacetylfentanyl and cyclopropylfentanyl are two of the newest illicit opioids that are infiltrating the heroin market. Methoxyacetylfentanyl and cyclopropylfentanyl were reported by the Drug Enforcement Administration (DEA) in their third quarter report of 2017 to have been chemically identified seven and five times, respectively, from drug evidence analyzed by the DEA's lab system; Q3 was the first time cyclopropylfentanyl was identified by the DEA's lab system, while methoxyacetylfentanyl was reported one time in Q2 2017. A method was developed using liquid chromatography tandem mass spectrometry for the quantitation of fentanyl, norfentanyl and 17 fentanyl analogs: furanylfentanyl, butyrylfentanyl, despropionylfentanyl (4-ANPP), methoxyacetylfentanyl, tetrahydrofuran fentanyl, fluoro-isobutyrylfentanyl, acrylfentanyl, para-fluorofentanyl, ortho-fluorofentanyl, carfentanil, beta-methylfentanyl, isobutyrylfentanyl, para-methylfentanyl, cyclopentylfentanyl, cyclopropylfentanyl, beta-hydroxyfentanyl and alpha-methylfentanyl. The calibration range for all compounds was 0.1-100 ng/mL. Blood samples from 42 postmortem cases involving cyclopropylfentanyl and methoxyacetylfentanyl from Florida, Illinois, Michigan and Tennessee were submitted for toxicological analysis. The mean and median concentration for the cases testing positive for cyclopropylfentanyl (n = 32) was 15.3 (+/- 11.9) ng/mL and 12.3 ng/mL, respectively, with a range of 1.4-43.3 ng/mL. The mean (+/- SD) and median concentrations for the 11 cases quantitatively confirmed (3 cases were below the limit of quantitation) for methoxyacetylfentanyl was 17.7 (+/- 11.4) ng/mL and 15.1 ng/mL respectively, with a range of 0.21-39.9 ng/mL. These novel illicit substances typically are outside the scope of routine drug testing by hospitals and toxicology laboratories or below the sensitivity levels for the detection of these substances in biological specimens. These compounds have not previously been studied in humans; therefore, it is significant to be able to associate the pharmacological effects derived from case reports to the quantitative values found in the postmortem specimens.