A universal approach for improving the limit of detection for fentanyl and fentanyl derivatives in urine

项目总结 处方药相关的不良死亡是美国第四大死因。阿片类药物 止痛药是最常被滥用的药物类别，占所有药物过量的66%以上。 2016年的死亡人数。死于过量处方阿片类药物的人数比死于所有其他药物的总和还要多 (包括非法药物)。芬太尼是最广泛滥用的处方阿片类药物。它通常是用来治疗的 严重的疼痛，但效力是海洛因的40-50倍，并带有过量服药的高风险。除了存在之外 作为常规药物筛查的一部分，芬太尼是美国国家安全委员会筛查小组的成员 (用于工作场所筛查)，并越来越多地被其他联邦准则采用，例如 2017年的运输，以确保遵守负责任的处方做法和患者遵守 阿片类药物治疗。然而，目前用于检测芬太尼的测试存在问题。最初的“关注点” 检测通常又快又简单，就像试纸测试一样，但人们普遍认为它们缺乏特异性和 敏感度。注意事项测试在区分芬太尼及其衍生化合物和 有很高的假阳性和阴性率，有时高达30%。出于这个原因，积极的结果 从这些初步测试开始，必须在较大的临床实验室通过以下方式接受第二轮“确认性”测试 气相或液质联用。这一增加的步骤效率不高；这意味着更多的时间 (有时结果需要数周时间)、费用和积压。据美国药品监督管理局报道， 国家法医实验室信息系统(NFLIS)，处理了数十万个样本 每年，这一数字预计还会上升。更好、更敏感、更高效的药物测试能力 需要解决日益严重的全国阿片类药物流行问题。 根据这一明确的需求和Hear倡议的目标，Ceres Nanoscience，Inc.提出了一种 第一阶段SBIR，以演示其智能纳米颗粒技术(NanoTrap®)作为样本的可行性 浓缩器，使芬太尼及其衍生物的检测更快、更便宜、更有鉴别力 大量的尿液。在有希望的原则证明数据的支持下，这项倡议的具体目标是： 目的1：论证纳米捕集颗粒预浓缩的可行性及改进芬太尼检测方法 和目标2：确定适合样品的纳米捕捉器工作流程 多环境下的处理，即中量参考实验室和大容量验证性测试实验室 工作流程。这些研究将为旨在扩大NanoTrap能力的未来第二阶段工作提供信息 芬太尼测试和评估其在真实世界药物测试实验室的位置。最终，如果成功， 将纳米捕捉器颗粒配制成可用于临床、商业和法医学的平台 用于多种芬太尼衍生物、类似物或合成变种的样品浓缩的预测试实验室 可以转化为更全面、更有效的测试实践，降低药物测试的成本，并最终 帮助解决目前的技术瓶颈，这些瓶颈只会阻碍抗击这一全国性流行病的努力。

PROJECT SUMMARY Prescription drug-related adverse deaths rank as the fourth-leading cause of death in the United States. Opioid pain relievers constitute the most commonly abused class of drugs, involved in over 66% of all drug overdose deaths in 2016. More people die from overdoses of prescription opioids than from all other drugs combined (including illegal drugs). Fentanyl is the most widely misused prescription opioid. It is often prescribed to treat severe pain but is 40–50 times more potent than heroin and carries a high risk of overdose. In addition to being included as part of the routine drug screening, fentanyl is on the screening panel of the National Safety Council (for workplace screening) and is being increasingly adopted for other federal guidelines, e.g., the Department of Transportation in 2017, to ensure compliance with responsible prescribing practices and patient adherence to opioid therapy. The tests currently used to detect fentanyl, however, are problematic. The initial, “point of care” tests are often quick and simple, like a dipstick test, but are widely recognized for their lack of specificity and sensitivity. Point of care tests are not great at distinguishing between fentanyl and its derivative compounds and have high false-positive and -negative rates, sometimes as high as 30%. For this reason, the positive results from these initial tests have to undergo a second round of “confirmatory” testing at larger clinical laboratories via either gas or liquid chromatography-mass spectrometry. This added step is not efficient; it means greater time (sometimes weeks for results), expense, and back log. As reported by the Drug Enforcement Administration’s National Forensic Laboratory Information System (NFLIS), hundreds of thousands of samples are processed each year, and this number is expected to rise. Better, more sensitive, and efficient drug testing capabilities are needed to address the growing national opioid epidemic. In line with this clear need and the objectives of the HEAL initiative, Ceres Nanoscience, Inc. proposes a Phase I SBIR to demonstrate the feasibility of its smart nanoparticle technology (Nanotrap®) as a sample concentrator to enable the faster, cheaper, and more discerning detection of fentanyl and its derivatives from large volumes of urine. Supported by promising proof-of-principle data, the specific aims for this initiative are to: Aim 1: demonstrate the feasibility of Nanotrap particles to pre-concentrate and improve the detection of fentanyl and its derivatives from large-volume urine samples; and Aim 2: identify a Nanotrap workflow suitable for sample processing in multiple contexts, i.e., medium-volume reference lab and high-volume confirmatory testing lab workflows. These studies will inform a future Phase II effort aimed at expanding the capabilities of the Nanotrap fentanyl assay and evaluating its placement in real-world drug testing laboratories. Ultimately, if successful, the formulation of Nanotrap particles into a platform that could be used by clinical, commercial, and forensic laboratories for pre-testing sample enrichment of multiple fentanyl derivatives, analogs, or synthetic variants could translate into more comprehensive, efficient testing practices, reduce costs for drug testing, and ultimately help to address the current technical bottlenecks that are only hindering efforts to combat this national epidemic.