HAIR ANALYSIS TO MONITOR DRUG ABUSE TREATMENTS

监测治疗依从性和药物使用是 药物滥用治疗方案和新治疗方法的临床试验 养生法尿液药物检测经常用于这些目的。头发 可以用作药物和其它物质的储存器， 更灵敏、更宽的药物暴露检测窗口。的 某些药物及其代谢产物的存在已被证明， 当血浆和尿液药物浓度不 可测量的因此，有可能重建一个 通过分析个体毛发片段来评估个体的药物暴露。的 该项目的目标是获得有关适用性的知识， 用于治疗药物依从性的人类毛发片段的定量分析 以及在药物治疗方案的临床试验中滥用药物的情况。 将特别强调确定和使用 特定的标记物质，以建立头发中的时间参考点。到 为了实现这些目标，提出了以下具体目标。 l）开发超灵敏和特异性的定性和定量方法， 治疗和潜在标记物的定量测量 人的头发具体而言，我们将制定敏感和具体的 使用GC/MS检测和定量处理的程序 药物如丁丙诺啡和L-α-乙酰美沙酮以及它们的 人类头发中的代谢物。我们还将制定敏感和具体的 使用紫外分光光度法和GC/MS进行检测的程序， 人体内潜在标记物非那吡啶的定量测定 头发 2)进行基础药代动力学研究， 在体外使用毛发中的治疗药物和潜在标记物质 技术和人类受试者。首先我们要确定 在体外培养的灯泡可以用作模型来评估掺入 的标记物质，如非那吡啶到头发中的存在下， 滥用药物（吗啡）和治疗药物（丁丙诺啡）。然后我们 将确定是否可以将标记物质给予人类受试者 指定的、已知的间隔，以便在毛发中建立参考点 在此之间可以定量测量药物使用情况。 3)为了确定毛发片段的定量分析是否可用于 在临床研究中评估药物滥用和治疗依从性。 具体地说，我们将确定是否管理一个标记， 可使用诸如非那吡啶物质来建立参照物 在人类头发中，药物使用和治疗依从性之间的点可以 在入组临床药物试验或药物治疗的受试者中进行测量 程序. 初步数据表明，我们能够执行所有 这一建议的各个方面，我们显然将能够从 分析方法开发，用于治疗药物的体外研究， 标记物掺入，用于标记物的人体研究 和治疗药物。

Monitoring treatment compliance and drug use is an important aspect of drug-abuse treatment programs and clinical trials for new treatment regimens. Urine drug testing is frequently used for these purposes. Hair may serve as a reservoir for drugs and other substances and may provide a more sensitive and broader window of detection for drug exposure. The presence of certain drugs and their metabolites has been demonstrated in human hair at times when plasma and urine drug concentrations are not measurable. Therefore, it may be possible to reconstruct a history of an individual's drug exposure via analysis of individual hair segments. The goal of this project is to acquire knowledge regarding the suitability of quantitative analysis of human hair segments for treatment drug compliance and use of abused-drugs in clinical trials of drug treatment regimens. Particular emphasis will be placed on the identification and use of a specific marker substance to establish time reference points in hair. To achieve these objectives the following specific aims are proposed. l) To develop ultra-sensitive and specific methods for the qualitative and quantitative measurement of treatment and potential marker substances in human hair. Specifically, we will develop sensitive and specific procedures using GC/MS for the detection and quantitation of treatment drugs such as buprenorphine and l-alpha-acetylmethadol and their metabolites in human hair. We will also develop sensitive and specific procedures using UV spectrophotometry and GC/MS for the detection and quantitation of a potential marker substance, phenazopyridine, in human hair. 2) To perform basic pharmacokinetic studies of the disposition of treatment drugs and potential marker substances in hair using in vitro techniques and in human subjects. First, we will determine if viable hair bulbs, held in vitro, can be used as a model to evaluate the incorporation of a marker substance such as phenazopyridine into hair in the presence of an abused drug (morphine) and a treatment drug (buprenorphine). Then, we will determine if the marker substance can be given to human subjects at specified, known intervals in order to establish reference points in hair between which drug use can be quantitatively measured. 3) To determine if quantitative analysis of hair segments can be used to evaluate drug-abuse and treatment compliance in a clinical study. Specifically, we will determine if the administration of a marker substance such as phenazopyridine can be used to establish reference points in human hair between which drug use and treatment compliance can be measured in subjects enrolled in clinical drug trials or drug treatment programs. Preliminary data presented demonstrate that we are able to perform all aspects of this proposal and that we will clearly be able to progress from analytical methods development, to in vitro studies of treatment drug and marker substance incorporation, to human studies with marker substances and treatment drugs.