权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Separation and resolution of bioactive compounds, such as drug, utilizing hair roots as a specimen

以发根为标本分离和解析药物等生物活性化合物

基本信息

批准号：
15590047
负责人：
TOYO'OKA Toshimasa
金额：
$ 2.3万
依托单位：
University of Shizuoka
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

It is well known that many compounds are accumulated in hair. Thus, the hair analysis provides one important means for determining individual past history of long-term chemical exposure. In spite of many papers regarding hair analysis, the studies of drug disposition in the hair root are very rare, because it is believed that the permeation of drugs into the hair from circulated blood is very slow. However, recent research has shown that administered drugs are relatively promptly incorporated into the hair shaft via the hair roots. The results suggest the possibility of drug monitoring in hair roots shortly after drug administration, similar to drug monitoring using blood.In the present studies, bioactive compounds such as drugs and biogenic amines were determined by HPLC coupled with electrospray ionization-mass spectrometry (ESI-MS). The proposed procedure was applied to the determination in hair shaft of Dark Agouti rats after intraperitoneal (i.p.) administration of benzodiazepines … More (triazolam, alprazolam, estazolam and midazolam). Various metabolites accompanied with parent drugs were identified in the hair shaft. The time course studies of parent drugs and the metabolites in both hair root and plasma were also carried out after single i.p. administration of benzodiazepines. The results suggested that the concentrations of parent drugs and the metabolites in the hair samples were mainly dependent upon those in the plasma.Consequently, investigation of the fate of a drug in the hair roots and a comparison with that in the plasma seem to be important in order to elucidate drug disposition in hair and interpret the retrospective drug exposure.Sensitive determination of histamine (HA) in hair was also carried out by column-switching HPLC-ESI-MS. HA was labeled with excess amounts of DBD-F at 60℃ for 30 min in a basic medium. The proposed method was applied to HA determination in the hair of Dark Agouti rats and healthy volunteers. The determination of HA in the plasma of rats and humans was also successfully performed by this method. Because the proposed method provides good precision and trace detection of HA in hair, the analytical technique seems to be applicable for the determination of various biogenic amines in hair. Less

众所周知，头发中积聚了许多化合物。因此，头发分析为确定个人过去长期接触化学物质的历史提供了一种重要的手段。尽管有关毛发分析的论文很多，但关于药物在毛发根部的分布的研究很少，因为人们认为药物从循环血液渗透到头发中的速度很慢。然而，最近的研究表明，给药的药物通过毛根相对迅速地结合到毛干中。结果表明，在给药后不久，毛根中的药物监测是可能的，类似于用血液监测药物。在本研究中，药物和生物胺等生物活性化合物被用高效液相色谱-电喷雾电离-质谱仪(ESI-MS)联用测定。将该方法应用于黑腹大鼠(I.P.)毛干的测定。苯二氮卓类药物…的给药更多(三唑仑、阿普唑仑、艾司唑仑和咪达唑仑)。在毛干中发现了与母体药物伴生的各种代谢物。单次腹腔注射后，还进行了原药及其在毛根和血浆中代谢物的时程研究。苯二氮卓类药物的给药。结果表明，毛发中母体药物和代谢物的浓度主要取决于血浆中的药物浓度。因此，研究药物在毛根中的去向并与血浆中的药物进行比较，对于阐明药物在头发中的分布和解释药物的回溯性暴露具有重要意义。用过量的DBD-F标记HA，在碱性介质中60℃作用30min。将该方法应用于Dark Agti大鼠和健康志愿者头发中HA的测定。用该方法也成功地测定了大鼠和人血浆中的HA。由于该方法具有良好的精密度和对头发中HA的痕量检测，因此该分析技术似乎适用于头发中各种生物胺的测定。较少