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

项目摘要 处方药相关的不良死亡是美国第四大死亡原因。阿片 止痛药是最常被滥用的一类药物，占所有药物过量的66%以上 2016年死亡。更多的人死于过量的处方阿片类药物，而不是所有其他药物的总和 （包括非法毒品）。芬太尼是最广泛滥用的处方阿片类药物。它经常被用来治疗 它会引起剧烈疼痛，但比海洛因强40 - 50倍，而且过量服用的风险很高。除了是 作为常规药物筛选的一部分，芬太尼是国家安全理事会筛选小组的成员 (for工作场所筛查），并且越来越多地被其他联邦指南采用，例如，部 2017年的运输，以确保遵守负责任的处方实践和患者遵守 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“护理点” 测试通常是快速和简单的，如试纸测试，但被广泛认为是缺乏特异性， 灵敏度护理点测试在区分芬太尼及其衍生化合物方面并不出色， 有很高的假阳性和假阴性率，有时高达30%。因此，积极的结果 从这些初步测试中，必须在较大的临床实验室进行第二轮"确认"测试， 气相或液相色谱-质谱法。这一增加的步骤效率不高;这意味着更多的时间 （有时几周的结果），费用和积压的日志。据美国缉毒局（Drug Enforcement Administration）报道， 国家法医实验室信息系统（NFLIS），处理数十万样本 每年，而且这个数字预计还会上升。更好、更灵敏、更高效的药物检测能力， 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HEAL倡议的目标，Ceres Nanoscience，Inc.提出了一种 第一阶段SBIR，以证明其智能纳米颗粒技术（Nanotrap®）作为样本的可行性 浓缩器，使更快，更便宜，更挑剔的检测芬太尼及其衍生物， 大量的尿液。在有希望的原理证明数据的支持下，这一举措的具体目标是： 目的1：证明Nanotrap颗粒预浓缩和改善芬太尼检测的可行性 目标2：确定适用于样品分析的Nanotrap工作流程 在多个上下文中处理，即，中容量参考实验室和高容量确证性检测实验室 工作流程。这些研究将为未来旨在扩大Nanotrap能力的第二阶段工作提供信息 芬太尼含量测定和评估其在现实世界的药物检测实验室的位置。最终，如果成功， 将Nanotrap颗粒配制成可用于临床、商业和法医的平台 用于预测试多种芬太尼衍生物、类似物或合成变体的样品富集的实验室 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，这些瓶颈只会阻碍防治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.