Quantitative Drug Surveillance System Development

描述（由申请人提供）：药物滥用继续对公共卫生产生重大影响。然而，经过验证的定量药物滥用监测工具是有限的。近年来，若干国家药物滥用监测系统已停止运作或被大幅度削减。本提案旨在通过制定方法并确定药物监测系统的可行性，该系统基于对非法药物、其他药物使用指标（包括代谢物和合成前体）以及进入处理人类废物的城市污水处理厂（WWTP）的原始进水中的人类生物标志物进行量化，从而解决这些局限性。污水处理厂有已知的集水区，具有特定的地理边界、人口估计和容量流量，可以分析不同时间和地点之间社区药物排放的趋势。本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（非法和药物）以及选定的代谢物和人类群体生物标志物一起进行量化。目的：1)开发和验证一种敏感和选择性的分析方法，用于定量进入污水处理厂的原料进水24小时内的甲基苯丙胺、其他非法药物和药物的浓度；2)制定从各种污水处理厂获取样品的程序；3)在人均和社区基础上确定药物排泄的地理和时间（季节、一周中的哪一天）变异性，以描述使用模式并制定最有效的抽样框架；4)确定实测药物排放估计值与其他用药指标数据的相关性。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、基于时间的采样计划，包括季节和日间变化，至少获得52个样本。甲基苯丙胺和其他滥用药物很容易通过液相色谱/串联质谱法检测和唯一识别。污水处理厂覆盖了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存在很大的地理差异。我们的建议得到了不同的当地利益相关者的支持，包括公共卫生、药物治疗、执法部门和污水处理厂管理者。本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污水排放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)为地方规划者提供经过验证的定量研究结果，可用于为预防和干预工作的分配决策提供信息，并用于结果评估；3)环境化学家改进检测合法和非法药物的分析方法。4)评估其他地理区域，5)进行紧急疫情调查，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：本提案在内容和方法上都直接涉及公共卫生。药物滥用对公共健康造成严重后果，包括由于使用和滥用合法和非法药物而造成的发病率和死亡率。在方法学上，该建议提出了一种低成本的方法，用于监测社区一级的药物滥用趋势，以及开展疫情调查的一种手段。

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.