DISPOSITION OF DRUGS OF ABUSE INTO HAIR

对滥用药物的毛发的分析在毒理学中很有意义，而且 确定药物滥用治疗患者的依从性或再犯率 计划，为流行性感冒的流行病学研究提供科学标记 滥用药物，因害怕被发现而对吸毒起威慑作用；以及 协助检测新生儿可能接触毒品的药物。 在母亲怀孕期间和新生儿出生时进行检测。它 很可能在头发中检测到药物时，血浆 不包含可测量的药物浓度。因此，有一个 更需要建立剂量的基本药理学原则-- 滥用药物在人体内浓度的反应和时间反应 头发。为了确立这些原则，本项目的目标是：1) 开发超灵敏、选择性和可靠的气相色谱/质谱仪 光谱分析方法测量头发中滥用药物的情况。每种方法都将 被评估为去除表面吸附的污染物，酶或 对头发进行碱性消化，选择性提取药物和/或 代谢物，将药物转化为适合GC/MS的衍生物 用气相色谱/离子联用法分析、分析衍生药物 陷阱质谱学；2)开发和验证In的相关模型 人头发和人头皮皮肤(含头发)的体外培养 移植到裸鼠身上。含有毛发的人头皮皮肤模型 将通过以下方式验证剂量-反应和时间-反应关系 在人类受试者中进行了类似的研究。这个模型将被用于研究，在 详细说明控制头发中药物浓度的因素；以及3) 建立滥用药物药代动力学研究模型 在人类受试者的头发里。可待因将用于男性和 女性受试者在单次、递增剂量和多次剂量下 确定药物的量效关系和时间效应关系 头发中的浓度。头发颜色与人种和民族的影响 头发中药物浓度的背景也将被确定。 与这项提案一起提供的初步数据表明，我们能够 为了量化从海洛因使用者那里获得的人类头发中的吗啡 可以将含有毛囊的人类头皮移植到裸鼠身上。 实现上述目标的实验将为细心的人提供数据， 药物处置控制因素的科学研究 对人类头发的虐待。

The analysis of hair for drugs of abuse is of interest in toxicology, and to determine compliance or recidivism in patients in drug-abuse treatment programs, to provide a scientific marker for epidemiological studies of drug abuse, to serve as a deterrent to drug usage by fear of detection, and to aid in the detection of potential drug exposure in newborns by drug detection in the mother during pregnancy and in the newborn at birth. It is probable that drugs can be detected in hair at times when the plasma does not contain measurable concentrations of drugs. Thus, there is a greater need to establish the basic pharmacologic principles of dose- response and time-response for the concentration of drugs of abuse in human hair. To establish these principles the aims of this project are: 1) To develop ultra-sensitive, selective and reliable gas chromatography/mass spectrometry methods to measure drugs of abuse in hair. Each method will be evaluated for removal of surface-absorbed contaminants, enzymatic or alkaline digestion of hair, selective extraction of drugs and/or metabolites, conversion of the drugs to derivatives well-suited for GC/MS analysis, and analysis of the derivatized drugs by gas chromatography/ion trap mass spectrometry; 2) To develop and validate relevant models of in vitro human hair culture and of human scalp skin (containing hair) transplanted to nude mice. The model of human scalp skin containing hair will be validated for dose-response and time-response relationships by similar studies in human subjects. This model will be used to study, in detail, the factors that control the concentration of drugs in hair; and 3) To develop a model for the study of the pharmacokinetics of drugs of abuse in the hair of human subjects. Codeine will be administrated to male and female human subjects in single, increasing doses and multiple doses to determine the dose-response and time-response relationships with drug concentrations in hair. The effect of hair color and racial and ethnic background on drug concentration in hair will also be determined. Preliminary data presented with this proposal demonstrate that we are able to quantitate morphine in human hair obtained from heroin users and that we are able graft human scalp skin, containing hair follicles, to nude mice. Experiments to achieve the above aims will provide data for the careful, scientific study of the factors controlling the disposition of drugs of abuse in human hair.