节点文献
化学发光新体系在药物分析中的应用研究
Study on Analysis of Pharmaceutical Using New CL System
【作者】 李丽清；
【导师】 孙汉文；
【作者基本信息】 河北大学 ， 分析化学， 2007， 博士
【摘要】 本研究主要集中于两个方面,一方面是发现新的化学发光反应,建立新的化学发光分析方法,研究其应用于实际样品分析的可行性,另一方面是将电化学发光检测技术应用于毛细管电泳分析系统,以克服化学发光分析选择性差的不足。本论文主要研究内容如下：1化学发光新体系在抗肿瘤药物分析中的应用研究本论文将流动注射新技术应用于化学发光分析,对影响化学发光强度的诸因素进行了实验和探讨,建立了流动注射化学发光分析羟基喜树碱、丝裂霉素、阿霉素、氟尿嘧啶、6-巯基嘌呤、氨基蝶呤等抗肿瘤药物的化学发光分析新方法,测定以上物质的检出限分别6×10-9g mL-1、6×10-9g mL-1、6×10-8g mL-1、6×10-8g mL-1、6×10-9g mL-1、6×10-9g mL-1，线性范围分别为1.0×10-8～6.0×10-5g mL-1、1.0×10-8-6.0×10-5g mL-1 1.0×10-7～1.0x10-4gmL-1、1.0×10-7～8.0×10-5gmL-1、1.0×10-8～8.0×10-5gmL-1、1.0×10-8～6.0×10-5g mL-1。这些方法灵敏度高、线性范围宽、仪器设备简单、操作方便、可靠,为研究药物代谢提供了有效的分析手段。并对化学发光反应机理作了初步的探讨。2化学发光新体系在喹诺酮类药物分析中的应用研究本论文研究的目的在于建立一种灵敏度高、可靠性好的喹诺酮类抗生素的检测方法,以满足生物体内或自然环境中低含量的此类物质的分析测定要求。因此本文重点研究了氧氟沙星、洛美沙星、环丙沙星和诺氟沙星这4种常用喹诺酮类药物的化学发光分析新方法,其检出限分别为7×10-9g mL-1、3×10-9g mL-1、4×10-8g mL-1、6×10-9g mL-1,线性范围分别为2.0×10-8～6.0×10-6g mL-1、1.0×10-8～6.0×10-5g mL-1、1.0×10-8～1.0×10-5g mL-1、1.0×10-8～6.0×10-5g mL-1、并将这些方法分别应用于药剂和体液中喹诺酮类药物的分析,初步探讨了可能的化学发光机理。3镝离子敏化化学发光新体系在药物分析中的应用研究我们在实验中发现,稀土离子Dy3+可以大大提高化学发光强度,据此建立了Dy3+敏化化学发光新体系,探讨了该化学发光体系的发光机理。测定了培氟沙星、依诺沙星、氟罗沙星、吡哌酸和依诺沙星等喹诺酮类药物,测定这些药物的线性范围分别为1.0×10-9～8.0×10-6g mL-1、1.0×10-9～1.0×10-5g mL-1、1.0×10-9～6.0×10-5g mL-1、1.0×10-9～8.0×10-6g mL-1、1.0×10-9～8.0×10-6g mL-1、检出限分别为6×10-10g mL-1、3×10-10g mL-3×10-10g mL-1、6×10-10g mL-1、4×10-10g mL-1。这些方法具有灵敏度高、仪器设备操作简单、无需光源、无背景散射等背景干扰的优点,尤其是与流动注射相结合,测定简单快速、重现性好。4毛细管电泳一电化学发光检测在药物分析中的应用研究本论文以毛细管电泳为分离手段,以电化学发光为检测手段,建立了CE-ECL同时检测脯氨酸和吡哌酸；利多卡因、脯氨酸和洛美沙星；普鲁卡因、布比卡因、加替沙星、恩诺沙星和培氟沙星的新方法。讨论了联吡啶钌浓度、检测电位、磷酸盐缓冲液浓度和pH值、进样电压和进样时间等实验参数对分离检测的影响。确定了测定的线性范围,并将这些方法成功的应用于实际样品的分析,结果令人满意。
【Abstract】 This investigation is dedicated to two purposes. One purpose is to find new CL reactions, establish new CL methods and study their applications to real samples. The other purpose is to improve the selectivity of the CL method by the combination of CE detection system with ECL detection technique. The main content of this article is as follows:1 Study on analysis of anticancer drugs using new CL systemAn analytical method consisting of flow-injection sampling and CL detection for determination of anticancer drugs, including hydroxycamptothecinum, mitomycin, adriamycin, fluorouracil,6-mercaptopurine and aminopterin is described. Under the optimum conditions, the proposed method has a liner range of 1.0×10-8～6.0×10-5g mL-1,1.0.0×10-8～6.0×10-5gmL-1, 1.0×10-7～1.0×10-4g mL-1,1.0×10-7～-8.0×10-5gmL-1,1.0×10-8～1.0×10-5g mL-1 and 1.0xl0-8～6.0×10-5gmL-1, with a detection limit of 6×10-9gmL-1,6×10-9gmL-1, 6×10-7gmL-1,3×10-8gmL-1,6.0×10-9gmL-1 and 6.0×10-9gmL-1 for thydroxycamptothecinum, mitomycin, adriamycin, fluorouracil,6-mercaptopurine and aminopterin, respectively. These new method can perform simple, sensitive, rapid and suitable for automatic and continuous analysis. The possible mechanism of the CL reaction was also proposed.2 Study on analysis of the fluoroquinolones using new CL systemOur purpose is to find new CL reactions, establish new CL methods and study their applications to real samples. A new CL method to determine fluoroquinolones such as ofloxacin, lomefloxacin, ciprofloxacin and norfloxacin with flow injection technique was developed. Under the optimum conditions, the linear ranges for the determination of ofloxacin, lomefloxacin, ciprofloxacin and norfloxacin were 2.0×10-8～6.0×10-6g mL-1,1.0×10-8～6.0×10-5g mL-1,1.0×10-8～1.0×10-5g mL-1 and 1.0×10-8～6.0×10-5g mL-1 with the limits of detection of 7×10-9g mL-1,3×10-9g mL-1,4×10-8g mL-1 and 6×10-9g mL-1, respectively. The method has been applied to the determination of fluoroquinolones in real samples and the results were in good agreement with those obtained by official method. The preliminary mechanism of the reactions was also investigated. 3 Study on dysprosium sensitized CL of pharmaceutical and its applicationIt was found that the weak CL produced from the reaction of fluoroquinolones with oxidant in acid solution could be strongly enhanced by dysprosium. The CL mechanism of this system was discussed. Based on this found, a new flow injection CL method is proposed for the determination of fluoroquinolones such as pefloxacine, enoxacin, fleroxacin, pipemidic acid and enoxacin. Under the optimum conditions, the linear ranges for the determination of pefloxacine, enoxacin, fleroxacin, pipemidic acid and enoxacin were 1.0×10-9～8.0×10-6gmL-1,1.0×10-9～8.0×10-5gmL-1,1.0×10-9～8.0×10-6g mL-1 and 1.0×10-9～8.0×10-6gmL-1 with the limits of detection of 6×10-10g mL-1, 3×10-10g mL-1,3×10-10g mL-1,6×10-10g mL-1 and 4×10-10g mL-1, respectively. There are many merits on CL such as simple cheap optical systems requiring no light sources which avoiding the effects of stray light and the instability of light sources, and thus providing low background with excellent sensitivity, wide linear range, rapidity, simplicity and so on.4 Study on capillary electrophoresis with electrochemiluminescence detection of pharmaceutical and its applicationA high-performance capillary electrophoresis with electrochemiluminescence detection （CE-ECL） method has been applied for the determination of Pharmaceuticals, including proline, pipemidic acid, lidocaine, lomefloxacin, procaine, bupivacaine, gatifloxacin, enrofloxacin and pefloxacin in real samples. The effects of several factors such as the acidity and concentration of running buffer, the separation voltage, the applied potential and the injection time on CE-ECL were investigated. Under the optimum conditions, the linear ranges for the determination of these pharmaceuticals were investigated. The method had been successfully applied to analyze these components in real-life samples, and the assay results were satisfactory. The new method can perform simple, sensitive, rapid and suitable for automatic and continuous analysis.
【Key words】 Chemiluminescence； capillary electrophoresis with electrochemiluminescence； anticancer drug； fluoroquinolone； lanthanide；