DISPOSITION OF DRUGS OF ABUSE INTO HUMAN HAIR

毛发中药物滥用的分析在毒理学上是有意义的， 确定药物滥用治疗患者的依从性或再犯率 方案，为流行病学研究提供一个科学的标志， 滥用药物，通过害怕被发现来威慑使用药物， 以帮助检测新生儿的潜在药物暴露， 在母亲怀孕期间和新生儿出生时进行检测。 它 当血浆中含有药物时， 不含可测量浓度的药物。 因此，有一个 更需要建立剂量的基本药理学原则- 人体药物滥用浓度的响应和时间响应 头发 为确立这些原则，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 分光光度法测量头发中的药物滥用。 每种方法将 评估表面吸附污染物、酶或 毛发的碱性消化，药物的选择性提取和/或 代谢物，药物转化为衍生物非常适合GC/MS 分析和通过气相色谱/离子色谱分析衍生化药物 阱质谱法; 2）开发和验证相关的模型， 离体人发培养物和人头皮皮肤（含头发） 移植到裸鼠身上。 含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的类似研究。 该模型将用于研究，在 详细地说，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中。 可待因将给予男性， 女性受试者接受单次、递增剂量和多次给药， 确定药物的剂量-反应和时间-反应关系 头发中的浓度。 头发颜色和种族的影响 还将测定毛发中药物浓度的背景。 初步数据显示，我们能够 从海洛因使用者的头发中定量吗啡， 能够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仔细， 控制药物处置因素的科学研究 人发中的滥用。

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.