HAIR ANALYSIS TO MONITOR DRUG ABUSE TREATMENTS

监测治疗依从性和药物使用情况是 药物滥用治疗方案和新疗法的临床试验 养生法。尿液药物检测经常用于这些目的。头发 可用作药物和其他物质的储存库，并可提供 对药物暴露更敏感和更广泛的检测窗口。这个 某些药物及其代谢物的存在已在 人的头发在血浆和尿液药物浓度不是 可测量的。因此，有可能重建一个 通过对个体毛发片段的分析，了解个体的药物暴露情况。这个 本项目的目标是获取有关以下方面的知识 治疗药物依从性的人发段定量分析 以及滥用药物在药物治疗方案临床试验中的使用。 将特别强调识别和使用 用于在头发中建立时间参考点的特定标记物质。至 为实现这些目标，现提出以下具体目标。 L)制定超灵敏和具体的定性和定量方法 治疗和潜在标志物的定量测定 人的头发。具体地说，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 丁丙诺啡、L-α-乙酰美沙醇等药物及其临床应用 人类头发中的代谢物。我们还将制定敏感和具体的 使用紫外分光光度和GC/MS检测程序和 人体内潜在标志物吩唑吡啶的定量研究 头发。 2)进行药物处置的基础药代动力学研究 治疗药物和潜在的头发标志物在体外的应用 技术和人类受试者。首先，我们将确定是否有可行的头发 在体外保存的鳞茎可以作为评估掺入的模型。 在存在的情况下，将诸如吩唑吡啶之类的标志物注入头发 滥用药物(吗啡)和治疗药物(丁丙诺啡)。然后，我们 将确定这种标记物质是否可以在 指定的已知间隔，以便在头发中建立参考点 在这两者之间可以定量测量药物使用情况。 3)确定是否可以使用毛段的定量分析来 在临床研究中评估药物滥用和治疗依从性。 具体地说，我们将确定标记的管理是否 可以使用诸如吩唑吡啶之类的物质来建立参考 人类头发上的点，药物使用和治疗依从性之间的点 在登记参加临床药物试验或药物治疗的受试者中进行测量 程序。 提供的初步数据表明，我们能够执行所有 这项提案的各个方面，我们显然将能够从 分析方法的发展，治疗药物和药物的体外研究 标记物质在人体研究中的应用 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.