The opioid crisis is linked to an increased misuse of fentanyl as well as fentanyl analogs that originate from the illicit drug market. Much of our current understanding of fentanyl and fentanyl analog use in our communities comes from postmortem toxicology findings. In the clinical settings of addiction medicine and pain management, where the opioid abuse potential is high, the use of fentanyl, as well as specific fentanyl analogs, may be underestimated due to limited plasma testing and limited availability of assays with suitable analytical sensitivity and selectivity to detect misuse of fentanyls. We report plasma and blood assays for 17 fentanyls (these include fentanyl, fentanyl analogs, fentanyl metabolites and synthetic precursors) in clinical, and medical examiner, casework. A mixed-mode solid phase extraction of diluted plasma or precipitated blood was optimized for maximum recovery of the fentanyls with minimized matrix effects. Analysis was performed using a Waters ACQUITY UPLC I-Class interfaced with a Waters Xevo TQ-S micro tandem quadrupole mass spectrometer. Method parameters were optimized and validated for precision, accuracy, carryover, linearity and matrix effects. Application studies were performed in postmortem blood obtained in 44 fentanyl-related fatalities and in serial plasma samples from 18 surgical patients receiving intravenous fentanyl therapy while undergoing parathyroidectomy. Fentanyls found in postmortem cases included fentanyl, norfentanyl, despropionyl-fentanyl (4-ANPP), beta-hydroxy fentanyl (β-OH fentanyl), acetyl fentanyl, acetyl norfentanyl, methoxyacetyl fentanyl, furanyl fentanyl, cyclopropyl fentanyl, and para-fluorobutyryl fentanyl, with fentanyl, norfentanyl, 4-ANPP and β-OH fentanyl predominating in frequency. Fentanyl concentrations ranged from 0.2 to 56 ng/mL and fentanyl was nearly always found with 4-ANPP, norfentanyl and β-OH fentanyl. Concentrations of other fentalogs ranged from <1 to 84 ng/mL (extrapolated). In the surgical cases, fentanyl was detected and quantified along with norfentanyl and β-OH fentanyl, but without detection of 4-ANPP in any of the samples. The association and relative concentrations of β-OH fentanyl, fentanyl and norfentanyl in the postmortem and clinical studies indicated a metabolic, rather than an illicit, source of β-OH fentanyl.

阿片类药物危机与芬太尼以及源自非法药物市场的芬太尼类似物的滥用增加有关。我们目前对我们社区中芬太尼和芬太尼类似物使用的大部分理解来自死后毒理学发现。在成瘾医学和疼痛管理的临床环境中，阿片类药物滥用的可能性很高，由于血浆检测有限和具有合适分析灵敏度和选择性的检测方法的可用性有限，芬太尼以及特定芬太尼类似物的使用可能被低估检测芬太尼的滥用。我们报告了 17 种芬太尼（包括芬太尼、芬太尼类似物、芬太尼代谢物和合成前体）的血浆和血液检测结果，用于临床、体检医师和个案工作。对稀释血浆或沉淀血液的混合模式固相萃取进行了优化，以最大限度地回收芬太尼，同时将基质效应降至最低。使用与 Waters Xevo TQ-S 微型串联四极杆质谱仪连接的 Waters ACQUITY UPLC I-Class 进行分析。针对精密度、准确度、残留、线性和基质效应对方法参数进行了优化和验证。在 44 名芬太尼相关死亡病例的死后血液和 18 名接受静脉注射芬太尼治疗并接受甲状旁腺切除术的外科患者的连续血浆样本中进行了应用研究。在死后案件中发现的芬太尼包括芬太尼、去甲芬太尼、去丙酰芬太尼 (4-ANPP)、β-羟基芬太尼 (β-OH 芬太尼)、乙酰芬太尼、乙酰基去甲芬太尼、甲氧基乙酰基芬太尼、呋喃基芬太尼、环丙基芬太尼和对氟丁酰芬太尼，其中芬太尼、去甲芬太尼、4-ANPP 和 β-OH 芬太尼在频率上占主导地位。芬太尼的浓度范围为 0.2 到 56 ng/mL，芬太尼几乎总是与 4-ANPP、去甲芬太尼和 β-OH 芬太尼一起被发现。其他芬他洛的浓度范围从 <1 到 84 ng/mL（外推）。在手术病例中，芬太尼与去甲芬太尼和 β-OH 芬太尼一起被检测和量化，但在任何样品中都没有检测到 4-ANPP。死后和临床研究中 β-OH 芬太尼、芬太尼和去甲芬太尼的关联和相对浓度表明 β-OH 芬太尼是代谢来源，而不是非法来源。芬太尼的浓度范围为 0.2 到 56 ng/mL，芬太尼几乎总是与 4-ANPP、去甲芬太尼和 β-OH 芬太尼一起被发现。其他芬他洛的浓度范围从 <1 到 84 ng/mL（外推）。在手术病例中，芬太尼与去甲芬太尼和 β-OH 芬太尼一起被检测和量化，但在任何样品中都没有检测到 4-ANPP。死后和临床研究中 β-OH 芬太尼、芬太尼和去甲芬太尼的关联和相对浓度表明 β-OH 芬太尼是代谢来源，而不是非法来源。芬太尼的浓度范围为 0.2 到 56 ng/mL，芬太尼几乎总是与 4-ANPP、去甲芬太尼和 β-OH 芬太尼一起被发现。其他芬他洛的浓度范围从 <1 到 84 ng/mL（外推）。在手术病例中，芬太尼与去甲芬太尼和 β-OH 芬太尼一起被检测和量化，但在任何样品中都没有检测到 4-ANPP。死后和临床研究中 β-OH 芬太尼、芬太尼和去甲芬太尼的关联和相对浓度表明 β-OH 芬太尼是代谢来源，而不是非法来源。但在任何样品中均未检测到 4-ANPP。死后和临床研究中 β-OH 芬太尼、芬太尼和去甲芬太尼的关联和相对浓度表明 β-OH 芬太尼是代谢来源，而不是非法来源。但在任何样品中均未检测到 4-ANPP。死后和临床研究中 β-OH 芬太尼、芬太尼和去甲芬太尼的关联和相对浓度表明 β-OH 芬太尼是代谢来源，而不是非法来源。