Quantitative Drug Surveillance System Development

描述(申请人提供)：滥用药物继续对公众健康造成严重后果。然而，有效的、定量的药物滥用监测工具是有限的。近年来，几个国家的药物滥用监测系统已经停止运行或大幅缩减。这项提案旨在通过制定方法并建立一个药物监测系统的可行性，以量化非法药物、包括代谢物和合成前体在内的其他药物使用指标以及进入处理人类排泄物的城市污水处理厂(WWTP)的原始进水中的人类生物标志物，从而解决这些限制。污水处理厂有已知的集水区，具有特定的地理边界、人口估计和体积流量，从而能够分析社区毒品排放随时间和地点之间的趋势。这项提案主要关注的物质是甲基苯丙胺，它将与其他几种滥用药物(非法和毒品)以及选定的代谢物和人类种群生物标志物一起进行量化。目的：1)制定和验证一种灵敏和选择性的分析方法，以量化24小时内甲基苯丙胺、其他非法药物和药物的浓度，以及流入污水处理厂的原始进水流量归一化组合；2)制定从不同的污水处理厂获取样本的程序；3)在人均和社区的基础上确定药物排泄量的地理和时间(季节性、星期几)变异性，以便描述使用模式并制定最佳效率的抽样框架；以及4)确定所测量的药物排放量估计数与其他药物使用指标数据之间的相关性。为了实现这些目标，我们建议从俄勒冈州和华盛顿州的20个污水处理厂收集24小时、流量标准化的原始进水样本，为期一年。每个污水处理厂将采用分层的、以时间为基础的抽样计划，并纳入季节性和日间变化，从每个污水处理厂最少抽取52个样本。甲基苯丙胺和其他滥用药物很容易被检测到，并可通过液相色谱/串联质谱仪进行唯一识别。WWTP覆盖俄勒冈州和华盛顿州的100多个城镇。目前的药物监测数据表明，整个太平洋西北地区的药物使用率在地理上存在很大的异质性。我们的建议得到了当地不同利益相关者的支持，包括公共卫生、药物治疗、执法和WWTP管理人员。R21的研究结果可用于1)提供研究工具，通过将污水处理厂的流入数据与其他地理编码数据联系起来，检查有关药物使用差异的一系列问题；2)为当地规划者提供经过验证的量化结果，这些结果可用于为预防和干预努力和结果评估的分配决策提供信息；3)由环境化学家改进分析方法，以检测合法和非法药物；4)评估其他地理区域；5)紧急疫情调查；以及6)为未来的纵向和地理分析创建基线数据。公共卫生相关性：该提案直接涉及公共卫生的内容和方法。药物滥用具有重大的公共健康后果，包括因使用和滥用合法和非法物质而导致的发病率和死亡率。从方法上讲，这项提议开发了一种监测社区一级药物滥用趋势的低成本方法，以及一种进行暴发调查的手段。

DESCRIPTION (provided by applicant): Drug abuse continues to have major public health consequences. Yet, validated, quantitative drug abuse surveillance tools are limited. Several national drug abuse surveillance systems have ceased operating or been substantially curtailed in recent years. This proposal aims to address these limitations by developing the methodology and establishing the feasibility of a drug-surveillance system based on quantifying illicit drugs, other drug-use indicators including metabolites and synthesis precursors, and human biomarkers in raw influent entering municipal wastewater treatment plants (WWTP) that process human waste. WWTPs have known catchment areas with specific geographic boundaries, population estimates, and volumetric flows that allow for the analysis of trends in community drug discharge over time and between locations. The primary substance of interest for this proposal is methamphetamine, which will be quantified along with several other drugs of abuse (illicit and pharmaceutical) along with selected metabolites and human population biomarkers. AIMS: 1) Develop and validate a sensitive and selective analytical method for quantifying the concentration of methamphetamine, other illicit and pharmaceutical drugs in 24 hr, flow-normalized composites of raw influent entering WWTPs; 2) Develop procedures for obtaining samples from a diverse set of WWTPs; 3) Determine the geographic and temporal (seasonal, day of week) variability of drug excretion on a per capita and community basis in order to describe use patterns and to develop sampling frames with optimal efficiency; and 4) Determine the correlation between measured drug discharge estimates and other drug use indicator data. To meet these aims, we propose to collect 24 hr, flow-normalized samples of raw influent from 20 WWTPs throughout Oregon and Washington for one year. A minimum of 52 samples will be obtained from each WWTP using a stratified, time-based sampling plan that will incorporate seasonal and interday variation. Methamphetamine and other drugs of abuse are readily detected and uniquely identifiable by liquid chromatography/tandem mass spectrometry. WWTPs provide coverage to more than 100 cities and towns in Oregon and Washington. Current drug surveillance data indicate substantial geographic heterogeneity in rates of drug use throughout the Pacific Northwest. Our proposal has the support of diverse, local stakeholders including public health, drug treatment, law enforcement, and WWTP managers. The findings of this R21 can be used 1) to provide research tools to examine a range of questions regarding differences in drug use by linking WWTP influent data to other geocoded data, 2) to provide local planners with validated, quantitative findings that can be used to inform allocation decisions for prevention and intervention efforts and for outcome evaluations, 3) by environmental chemists to refine analytical methods for detecting licit and illicit drugs, 4) to evaluate other geographic areas, 5) for emergent outbreak investigations, and 6) to create baseline data for future longitudinal and geographic analyses. PUBLIC HEALTH RELEVANCE: This proposal directly addresses public health both in terms of its content and methods. Drug abuse has substantial public health consequences including morbidity and mortality due to the use and abuse of both licit and illicit substances. Methodologically this proposal develops a low-cost method for monitoring community level drug abuse trends as well as a means to conduct outbreak investigations.