Camedda Nicola, Dagoli Sara, Anzillotti Luca, Cecchi Rossana
Department of Medicine and Surgery Legal Medicine University of Parma Parma Italy.
Department of Biochemical, Metabolic and Neural Sciences, Institute of Legal Medicine University of Modena and Reggio Emilia Modena Italy.
Anal Sci Adv. 2024 Dec 23;6(1):e202400038. doi: 10.1002/ansa.202400038. eCollection 2025 Jun.
Synthetic opioids are lab-synthesized substances that target the brain's opioid receptors, offering analgesic and sedative effects. Amongst them, fentanyl is one of the most widely used to intervene in chronic pain in moderate to severe cancer situations. Butyryl fentanyl (BF) is a novel synthetic opioid whose use is growing. Its potency is seven times that of morphine and, unlike fentanyl, BF can only be obtained through illegal sources. Fentanyl and its analogues are related to harmful intoxications and an increase in opioid-related mortality in many countries, such as in the United States and Europe in recent years. This work developed and validated an effective and sensitive method based on solid-phase extraction followed by gas chromatography-mass spectrometry (GC-MS) for the determination of fentanyl and BF in oral fluid samples. To the best of our knowledge, it is the first successful attempt to quantify these analytes using GC-MS with a limit of quantification (LOQ) of 1 ng/mL in OF. Intra-day and inter-day percentage coefficient of variation were found within 1%-3% and 1%-14%, respectively, while accuracy ranged from 92% to 102% at four concentration levels (lower LOQ [LLOQ], 3, 20, 40 ng/mL) in accordance with the established criteria. The absolute recovery values were in the range of 80.0%-100.0%. The method was linear for all analytes, with quadratic regression of calibration curves always higher than 0.99. The validated method demonstrated its great potential to detect and quantify fentanyl and its analogue in OF and it can be useful not only in forensic investigations of addiction histories but also in epidemiological studies on the spread of fentanyl and BF among workers and/or drivers.
合成阿片类药物是在实验室合成的物质，作用于大脑的阿片受体，具有镇痛和镇静作用。其中，芬太尼是用于干预中重度癌症慢性疼痛最广泛使用的药物之一。丁酰芬太尼（BF）是一种新型合成阿片类药物，其使用正在增加。它的效力是吗啡的七倍，与芬太尼不同，BF只能通过非法渠道获得。芬太尼及其类似物与许多国家的有害中毒和阿片类药物相关死亡率增加有关，例如近年来在美国和欧洲。这项工作开发并验证了一种基于固相萃取随后气相色谱 - 质谱联用（GC - MS）的有效且灵敏的方法，用于测定口腔液样本中的芬太尼和BF。据我们所知，这是首次成功尝试使用GC - MS对这些分析物进行定量，在口腔液中的定量限（LOQ）为1 ng/mL。日内和日间变异系数百分比分别在1% - 3%和1% - 14%以内，而在四个浓度水平（低于定量限[LLOQ]、3、20、40 ng/mL）下，根据既定标准，准确度范围为92%至102%。绝对回收率值在80.0% - 100.0%范围内。该方法对所有分析物均呈线性，校准曲线的二次回归始终高于0.99。经过验证的方法显示出其在检测和定量口腔液中芬太尼及其类似物方面的巨大潜力，它不仅可用于成瘾史的法医调查，还可用于芬太尼和BF在工人和/或司机中传播的流行病学研究。
