【作者】 甘婷婷；

【导师】 夏之宁；

【作者基本信息】 重庆大学 ， 药物化学， 2006， 硕士

【摘要】 通过现代分析手段,了解药物在体内的变化,对药物及其代谢物进行研究,获得药物代谢动力学的各种参数和转变、代谢的方式、途径等信息,有助于在生产、实验、临床等各个方面对所研究的药物的质量做出估计与评价,以及对药物的改进和开发做出贡献。随着药物分析新技术、新仪器的不断问世,体内药物的分析变得比以前要容易。发展并改进用于体内药物分析的方法,可以为药物的分析和质量控制、临床合理用药及新药的开发提供有力的工具。毛细管电泳用于体内药物分析时的优点是分离效率高,样品需要量少,对样品的预处理要求简单,应用范围广,能用于分离多种化合物如药物、氨基酸、肽和蛋白质、低聚核苷酸甚至整个细胞。但由于毛细管的内径通常只有100μm左右,采用光谱检测方法时,检测光程较短,使得毛细管电泳的检测灵敏度不如常规的分析方法液相色谱,在实际的应用中受到限制。本文以毛细管电泳与化学发光在线联用的方法为基础,在实验室自制了一台联用化学发光检测的毛细管电泳装置,结合毛细管电泳分离效率高和化学发光检测灵敏度高的优点,用于体内低浓度药物的分析检测的应用中证明。该方法的选择性强,采用合适的化学发光检测体系,生物样品内的药物能获得灵敏的检测,同时可避免不在该化学发光体系中产生发光信号的物质的干扰。本文首先对毛细管电泳和化学发光分析的基本理论进行了介绍,重点综述了毛细管电泳和化学发光联用的接口方式和二者联用在药物分析中应用的研究现状。然后将毛细管电泳-化学发光在线联用的方法用于药物制剂以及药物在实验动物体内的代谢物的分析。文章的主要研究内容如下:1.毛细管电泳-化学发光联用仪器的构建以及仪器性能的改进。建立了毛细管电泳与化学发光检测在线联用的仪器,对自组装仪器的性能进行考察并作了改进。并采用这台仪器对两种喹诺酮类药物加替沙星和甲磺酸帕珠沙星进行了分析。利用沙星类药物在luminol-H2O2发光体系中有较强的抑制作用,对这两种物质进行了检测,并分别对这两种药物制剂中有效成分的含量进行了测定。2.将本方法用于中药材苦参中的有效成分氧化苦参碱和中西药复方珍菊降压片中有效成分芦丁的分析。采用luminol-H2O2-KMnO4发光体系,氧化苦参碱在该体系中产生较强的抑制信号。通过考察毛细管电泳分离条件和发光条件,最终实现了中药苦参提取液中氧化苦参碱的分离并对其含量进行了测定。利用芦丁在luminol-H2O2-NaClO发光体系中有较强的抑制作用,对其进行了分析。考察毛细管电泳分离条件和发光条件,实现了珍菊降压片提取液中芦丁的分离和灵敏检测。更多还原

【Abstract】 It is of great significance to study drugs and their metabolites. According to the drug characteristics about their biotransformation in organism, information about drug distribution and metabolism was acquired. With this information, the way in which drug metabolized was comprehended. It provided useful suggestions and evaluated those drug qualities through many aspects studies, such as production, experiment and clinical processes of drugs. Besides, it contributed to drug modification and exploitation. With the development of new instruments and utilization of drug analytical techniques, researches on drug metabolism have become more and more convenient. Developing and improving methods that can be used in the analysis of drugs and their metabolites in organism could provide strong tools for drug assay and new drug exploitation.Obviously, capillary electrophoresis (CE) has many distinctive advantages when it is used to analyze drugs and their metabolites in organism, such as high resolution, low sample consumption, simple pretreatment procedure and so forth. However, the inner diameter in the capillary column is often only around 100 micrometer. Due to the short optical path, when CE is coupled with spectrometry, its detect sensitivity is not as satisfied as that of high performance liquid chromatography (HPLC). So CE is seldom seen in practical applications. The method of CE coupled with chemiluminescence (CL) was set up in this dissertation to analyze very low concentration drugs in organism. The coexistent components that have no CL response will not influence the analytical result.In the first part of this dissertation, basic theories of CE and CL were introduced, focusing on interfaces between CE and CL and the application of on-line CE coupled with CL for pharmaceutical analysis. Furthermore, this method was used to analyze several kinds of pharmaceutics and a drug metabolite. The main contents of the study are mentioned as below:1. The fabrication and functional improvement of the instrument of CE coupled with CL. A new CE-CL instrument was set up in the lab. For the purpose of investigating and improving this method, it was utilized in the analysis of pazufloxacin mesilate sodium chloride (PZLX) and gatifloxacin (GTLX). Within PZLX or GTLX in the running buffer, the CL signal of luminol-H2O2 was restricted distinctly. According to the relationship between intensity of the CL signal districted and the concentration of the two medicines respectively, their concentrations in pharmaceutics were obtained.更多还原