Université de Lorraine, CHRU-Nancy, Department of Clinical Pharmacology and Toxicology, F-54000, Nancy, France.
Université de Lorraine, CHRU-Nancy, Department of Clinical Pharmacology and Toxicology, F-54000, Nancy, France; Université de Lorraine, CNRS, IMoPA, F-54000 Nancy, France.
Forensic Sci Int. 2020 Dec;317:110437. doi: 10.1016/j.forsciint.2020.110437. Epub 2020 Sep 6.
Synthetic opioids (SO) associated with the recent alarming increase of deaths and intoxications in United States of America and Europe are not detected by the usual first-line opiates drug screening assays. We developed a liquid chromatography tandem mass spectrometry analytical method for the multiplex detection of 14 fentanyl analogues (2-furanylfentanyl, 4-ANPP, 4-methoxybutyrylfentanyl, acrylfentanyl, alfentanil, carfentanil, despropionyl-2-fluorofentanyl, fentanyl, methoxyacetylfentanyl, norfentanyl, ocfentanil, remifentanil, sufentanil and valerylfentanyl) and U-47700 in whole blood and urine samples. The method was validated according to the requirements of ISO 15189. A simple and fast liquid-liquid extraction (LLE) with De-Tox Tube-A was performed leading to better recovery of molecules in urine than in blood samples. Depending on the compound, the limits of detection (LODs) ranged from 0.01 to 0.10 ng/mL and from 0.02 to 0.05 ng/mL in whole blood and urine, respectively. Calibration curves were linear in the range 0.5-50.0 ng/mL and the limit of quantification (LOQ) ranged from 0.10 to 0.40 ng/mL in blood. Internal quality controls at 1 and 40 ng/mL showed intra-day and between-day precision and accuracy bias below 10% in urine and 15% in blood. The method was applied to the screening of 211 urine samples from patients admitted in emergency or addiction departments. The presence of legal fentanyl analogues in 5 urine samples was justified by their therapeutic use as analgesics. Only one patient was concerned by fentanyl misuse and addiction whereas no illegal SO was detected. This study is not in favor of a huge misuse of SO in the Lorraine region.
与美国和欧洲近期令人震惊的死亡和中毒事件相关的合成阿片类药物（SO）无法通过常用的一线阿片类药物药物筛选检测。我们开发了一种液相色谱串联质谱分析方法，用于多重检测 14 种芬太尼类似物（2-呋喃基芬太尼、4-ANPP、4-甲氧基丁酰芬太尼、丙烯芬太尼、阿芬太尼、卡芬太尼、去丙酰基-2-氟芬太尼、芬太尼、甲氧基乙酰芬太尼、诺芬太尼、奥芬太尼、瑞芬太尼、舒芬太尼和戊基芬太尼）和 U-47700 在全血和尿液样本中。该方法根据 ISO 15189 的要求进行了验证。使用 De-Tox Tube-A 进行了简单快速的液液萃取（LLE），导致分子在尿液中的回收率高于血液样本。根据化合物的不同，检测限（LOD）在全血和尿液中的范围分别为 0.01 至 0.10 ng/mL 和 0.02 至 0.05 ng/mL。校准曲线在 0.5-50.0 ng/mL 范围内呈线性，血液中的定量限（LOQ）范围为 0.10 至 0.40 ng/mL。在尿液中，1 和 40 ng/mL 的内部质量控制显示日内和日间精密度和准确度偏差低于 10%，在血液中低于 15%。该方法应用于 211 例急诊或成瘾科患者的尿液筛查。5 例尿液样本中合法芬太尼类似物的存在是合理的，因为它们作为镇痛药使用。只有一名患者存在芬太尼滥用和成瘾问题，而未检测到非法 SO。这项研究不支持洛林地区 SO 的大量滥用。
