HAIR ANALYSIS TO MONITOR DRUG ABUSE TREATMENTS

描述：(申请人摘要) 监测治疗依从性和疗效的改进方法是 新药物滥用治疗方案和临床试验的重要目标 治疗方案。监测怀孕期间的药物使用也是一种 重要的临床目标。与尿液、血浆和血液相比，头发可能 提供更长的窗口来监测药物和其他化合物，因为其 生长缓慢，药物可能永久滞留。.的存在 某些药物及其代谢物已在人类头发中被证实 无法测量血浆和尿液药物浓度的时间。这个 本项目的目标是获取有关以下方面的知识 用于药物检测的定量、节段性人发分析 在临床环境中暴露。将使用特定的标记物质来 在人类头发中建立参考点(相对于时间)。要实现 在这些目标中，提出了以下具体目标：(1)发展 毛发的LC/MS/MS定量分析方法 超灵敏和特定的程序使用液相色谱和 串联质谱学将被开发用于联合检测和 治疗药物(丁丙诺啡、1-α-乙酰美沙醇或 美沙酮)、滥用药物(吗啡、海洛因)和标志性物质 (吩唑吡啶或氧氟沙星)在头发中。此外，还具有针对性和选择性 将制定去污程序，将潜在的偏差降至最低 对于感兴趣的药物的头发的环境污染，并最大限度地 测量的定量药物浓度的可靠性。(2)至 确定头发的定量分析是否可以用来评估 累犯和治疗依从性。标记物质的给药 例如吩唑吡啶或氧氟沙星将用于建立参考 人类头发中药物使用和治疗依从性之间的点 临床药物滥用研究中的累犯率是可以衡量的。我们还将 确定头发中药物浓度的定量测量是否 取决于给药剂量和给药途径。(三)确定 头发的定量分析是否可以用来评估胎儿药物暴露 在接受药物治疗的孕妇中。具体来说，我们将确定 如果母亲接触一种治疗药物 孕期美沙酮和新生儿头发美沙酮浓度 在出生的时候。 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，去污研究，活体人体 和动物研究标记物质结合到毛发中，并 关于胎儿药物暴露的研究。

DESCRIPTION: (Applicant's Abstract) Improved methods to monitor treatment compliance and efficacy is an important goal of drug-abuse treatment programs and clinical trials for new treatment regimens. Monitoring drug use during pregnancy is also an important clinical goal. Compared to urine, plasma and blood, hair may provide a longer window to monitor for drugs and other compounds due to its slow growth and possible permanent retention of drugs. 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. The goal of this project is to acquire knowledge regarding the suitability of quantitative, segmental human hair analysis for determination of drug exposure in clinical settings. Specific marker substances will be used to establish reference points (with respect to time) in human hair. To achieve these objectives, the following specific aims are proposed: (1) To develop quantitative analytical methods for hair utilizing LC/MS/MS. Ultra-sensitive and specific procedures using liquid chromatography and tandem mass spectrometry will be developed for the combined detection and quantitation of a treatment drug (buprenorphine, 1-alpha-acetylmethadol, or methadone), drugs of abuse (morphine, heroin) and marker substances (phenazopyridine or ofloxacin) in hair. Also, specific and selective decontamination procedures will be developed to minimize the potential bias of environmental contamination of hair for drugs of interest and to maximize the reliability of measured quantitative drug concentrations. (2) To determine if quantitative analysis of hair can be used to evaluate recidivism and treatment compliance. Administration of a marker substance such as phenazopyridine or ofloxacin will be used to establish reference points in human hair between which drug use and treatment compliance or recidivism in clinical drug-abuse studies can be measured. We will also determine if quantitative measures of drug concentrations in hair are dependent upon the dose and route of drug administration. (3) To determine if quantitative analysis of hair can be used to evaluate fetal drug exposure in pregnant women receiving drug treatment. Specifically, we will determine if there is a relationship between maternal exposure to a treatment drug (methadone) during pregnancy and neonatal hair concentrations of methadone at birth. 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 decontamination studies, to in vivo human and animal studies of marker substance incorporation into hair, and to studies of fetal drug exposure.