DISPOSITION OF DRUGS OF ABUSE IN HUMAN HAIR

人类头发中滥用药物的处置

• 批准号: 2897882
• 负责人: DOUGLAS E ROLLINS
• 金额: $ 27.91万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-03-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2897882
• 关键词: athymic mouse; cell cycle; chemical binding; gender difference; hair; human tissue; immunocytochemistry; liquid chromatography; mass spectrometry; melanins; melanosomes; phencyclidine; pigmentation; scanning electron microscopy

DESCRIPTION: (Applicant's Abstract) The analysis of hair for drugs of abuse is the most rapidly growing area in drug detection. It also has the potential to be used to determine compliance or recidivism 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 fetuses by drug detection in the mother during pregnancy and in the newborn at birth. Drugs can be detected in hair at times when the plasma or urine does not contain measurable concentrations of drugs. During the previous grant period we have developed analytical methods to measure codeine, morphine cannabinoids, phenobarbital, MDMA, and methamphetamine in hair. We have also determined that codeine is incorporated into animal and human hair in a dose-proportional manner; that codeine and morphine, but not phenobarbital, are preferentially incorporated into black hair versus white hair; that there are specific binding sites for codeine and morphine in black, but not white, hair; that human hair grafted onto athymic mice will serve as a model for the incorporation of drugs of abuse; and that codeine can be detected in human hair within 30 minutes after a single dose, and continue to be detected in hair for at least 10 weeks. In this continuation, we will expand on these findings and develop new methods to study drug incorporation into hair. Specifically, we will, 1) develop analytical methods for measuring the unique metabolites of drugs of abuse in hair using LC/MSMS; 2) localize the distribution of drug binding in hair components using immunohistochemistry with electron microscopy visualization; 3) determine the relationship between the hair melanin concentration and drug incorporation into hair; 4) characterize the incorporation of PCP into hair and study its binding to isolated melanosomes; 5) determine the role of gender and hair color in drug incorporation into the hair of human subjects; and 6) determine, in human subjects, whether actively dividing hair-forming cells are required for drug incorporation. Experiments to achieve these aims will provide data for the careful scientific study of the factors controlling the disposition of drugs of abuse in human hair.

描述：（申请人摘要） 毛发滥用药物分析是增长最快的领域 在毒品检测方面。 它还有可能被用来确定 药物滥用治疗计划中的依从性或累犯，以提供 用于药物滥用流行病学研究的科学标记，以服务 通过害怕被发现来威慑吸毒，并帮助 通过药物检测来检测胎儿潜在的药物暴露 母亲在怀孕期间和新生儿出生时。 药物可以 当血浆或尿液中不含时，有时会在头发中检测到 可测量的药物浓度。 在上一个资助期间，我们开发了分析方法 测量可待因、吗啡大麻素、苯巴比妥、MDMA 和 头发中的甲基苯丙胺。 我们还确定可待因是 以剂量成比例的方式掺入动物和人类的头发中； 优先使用可待因和吗啡，但不使用苯巴比妥 融入黑发与白发；表示有具体的 黑色头发中可待因和吗啡的结合位点，但白色头发中没有； 将人类头发移植到无胸腺小鼠身上将作为模型 纳入滥用药物；可待因可以在 单次给药后 30 分钟内，并继续使用人的头发 在头发中检测到至少 10 周。 在此续篇中，我们将扩展这些发现并开发新的 研究药物掺入头发的方法。 具体来说，我们将， 1）开发测量独特代谢物的分析方法 使用 LC/MSMS 检测头发中的滥用药物； 2）本地化分布 使用电子免疫组织化学研究头发成分中的药物结合 显微镜可视化； 3）确定头发之间的关系 黑色素浓度和药物掺入头发； 4）表征 将五氯苯酚掺入头发并研究其与分离的 黑素体； 5）确定性别和发色在药物中的作用 融入人类受试者的头发中； 6) 确定，在 人类受试者，活跃分裂的毛发形成细胞是否 药物掺入所需的。 实现这些目标的实验将为仔细研究提供数据 控制药物处置因素的科学研究 滥用人类头发。