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芯片毛细管电泳在药物分析中的应用研究

Application of Microfluidic Chips for Pharmaceutical Analysis

【作者】 苑广信

【导师】 陈恒武;

【作者基本信息】 浙江大学 , 分析化学, 2006, 硕士

【摘要】 最近几年,以毛细管电泳为核心技术、以芯片为操作平台的芯片毛细管电泳技术迅速崛起,并成为微全化学分析系统(miniaturized total chemical analysis system,μTAS,又称芯片实验室,Lab—On—a—chip)的主流技术。由于芯片毛细管电泳耗样量少,分析速度快,并且便于微型化,所以在药物分析和生物领域中有很好的应用前景。本工作采用芯片毛细管电泳—激光诱导荧光检测方法,分别对麻黄碱类兴奋剂和抗肿瘤药物的分离检测进行了研究。 在第一章中,介绍了微流控芯片荧光检测的装置和特点,对衍生方式和荧光衍生试剂及分析特性进行了综述,并介绍了芯片毛细管电泳荧光检测法在药物分析中的应用。 在第二章中,本文采用芯片毛细管电泳激光诱导荧光检测系统对麻黄碱类兴奋剂的分离检测进行了研究。由于麻黄碱类兴奋剂本身没有荧光,采用7-chloro-4nitrobenzo-2-oax-1,3-diazole(NBD-Cl)做衍生试剂,分离了经NBD-Cl衍生的麻黄碱和伪麻黄碱,一次分离的时间小于90S,检测结果具有较好的精密度和线性关系。并将所建立的方法应用于尿中麻黄碱和伪麻黄碱的分离测定,取得满意的结果。 在第三章中,采用芯片毛细管电泳激光诱导荧光检测系统对抗肿瘤药物阿霉素和揉红霉素的分离检测进行了研究。当用自由区带毛细管电泳分离时,分离缓冲液中加入40%乙腈可显著提高柱效和灵敏度,从而实现了阿霉素和揉红霉素的快速分离和直接测定(无须衍生),一次分离的时间小于60秒,并取得了较好的重现性和检测限。

【Abstract】 In recently years, the chip-based capillary electrophoresis (CCE) has achieved great progress and becomes essential technique of the miniaturized total chemical analysis system(μTAS or Lab-On-a-chip). Thanks to the advantages such as low sample consume, quick analysis speed and easy to be miniaturized, CCE possesses promoting potential in analysis and the life science. In this text, two methods have been developed for the determinations of ephedrine dopes and of the anti-tumor medicine by means of a chip-based capillary electrophoresis system with laser-induced fluorescence detector(CCE-LIF).In the first chapter, the device and the characteristics of the CCE-LIF, the reagents and the methods of derivatization reaction were introduced,and the reports on application of CCE-LIF for pharmaceutical analysis were reviewed.In the second chapter, a method was developed for determination of ephedrine (EP) and pseudoephedrine (PEP) dopes with a CE-LIF. The dopes were derived with 7-chloro-4nitrobenzo-2-oax-1,3-diazole (NBD-C1) to form fluorescent products. EP and PEP can be base-line separated from the reagent components as well as the species existing in the urine within 90 seconds. There are good precision and linear relationship for both EP and EPE. Satisfactory recoveries were achieved when the developed method was used for determination of EP and PEP concentration spiked into human urine.In the third chapter, a method was developed for determination of anti-tumor medicine doxorubicin (DX) and daunorubicin (DAU) with a CCE-LIF. Addition of 40% acetonitrile into the borate running buffer could significantly improved the separation efficiency and enhanced the fluorescence detection sensitivity, resulting a base-line separation of the two drugs within 60 seconds. Satisfactory repeatability and the limits of detection(LOD) were achieved.

  • 【网络出版投稿人】 浙江大学
  • 【网络出版年期】2006年 08期
  • 【分类号】O658.9;TQ460.7
  • 【下载频次】293
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