【作者】 张小燕；

【导师】 张成孝；

【作者基本信息】 陕西师范大学 ， 分析化学， 2004， 硕士

【摘要】 本文在引言部分简要介绍了化学发光分析的发展概况、基本原理以及应用于药物分析的主要化学发光体系，综述了近十年来化学发光在药物分析中应用的研究进展。研究报告对鲁米诺体系的后续化学发光反应做了详细地研究，提出了鲁米诺体系的后续化学发光的反应机理。 药物分析是当今分析化学的一个重要的研究课题。流动注射化学发光分析法具有仪器设备简单、分析速度快、灵敏度高、线性范围宽等优点，所以越来越受到分析化学工作者的重视。本文基于鲁米诺体系的后续化学发光现象，建立了四种药物亚硫酸氢钠甲萘醌、双嘧达莫、异烟肼、抗坏血酸的化学发光分析法。 我们在实验中发现，将亚硫酸氢钠甲萘醌溶液注入鲁米诺与高碘酸钾化学发光反应结束后的混合溶液中可产生强的后续化学发光信号。在实验过程中，采用流动注射分析技术，对影响化学发光反应的诸因素（如混合管道的长度、反应介质的酸碱度、鲁米诺溶液的浓度、高碘酸钾的浓度等）进行了考察，从而建立了测定亚硫酸氢钠甲萘醌的化学发光分析法。该方法具有以下优点：（1）具有较高的灵敏度，根据IUPAC规定，计算得该方法的检出限为8×10¹⁰g／mL；（2）线性范围宽，化学发光分析信号与亚硫酸氢钠甲萘醌的浓度在2×10^-9～4×10^-5g／mL之间呈良好的线性关系；（3）方法的精密度好，对1×10^-6g／mL的亚硫酸氢钠甲萘醌进行11次平行测量，相对标准偏差小于0.5％。该法用于亚硫酸氢钠甲萘醌针剂中亚硫酸氢钠甲萘醌含量的测定，结果令人满意。本文在对该体系化学发光光谱、荧光光谱及其一系列反应特性的考察基础上，对该体系的发光机理进行了详细的研究，提出了鲁米诺的后续化学发光机理。 发现将含氮杂环的嘧啶类合成药物双嘧达莫溶液注入鲁米诺与铁氰化钾化学发光反应结束后的混合溶液中可产生强的后续化学发光信号。根据此实验现象并结合流动注射分析技术，建立了测定双嘧达莫的化学发光分析法。在优化的实验条件下，化学发光分析信号与双嘧达莫的浓度在1×10^-10～4×10^-7g／mL之间呈良好的线性关系。根据IUPAC规定，计算得该方法的检出限为6×10^-11g／mL。对1×10^-8g／mL的双嘧达莫进行7次平行测量，相对标准偏差为1.1％。该方法用于双嘧达莫片剂中双嘧达莫含量的测定，并与药典中标准方法进行对照，没有显著性差异。本文在对该体系化学发光光谱、荧光光谱及其一系列反应特性的考察基础上，对该体系的发光机理进行了详细的研究，提出了鲁米诺的后续化学发光机理。 实验发现将异烟脱溶液注入鲁米诺与高锰酸钾化学发光反应结束后的混合溶液中可产生强的后续化学发光信号。根据此实验现象并结合流动注射分析技术，建立了测定异烟胁的化学发光分析法。在优化的实验条件下，化学发光分析信号鸳鼻妞睽的被度友:义t0一名一I义[0一它而L之间呈良好的线性关系。根据IuPAc规定，计算得该方法的检出限为1 X10一sg/mL。对1 x10一6留mL的异烟胁进行7次平行测量，相对标准偏差为1.1%。该方法用于异烟脐片剂中异烟麟含量的测定，结果令人满意。本文在对该体系化学发光光谱、荧光光谱及其一系列反应特性的考察基础上，对该体系的发光机理进行了详细的研究，提出了鲁米诺的后续化学发光机理。 本文发现将抗坏血酸注入鲁米诺与铁氰化钾化学发光反应后的混合溶液中能产生一个强的化学发光信号，在实验的基础上对化学发光机理进行了详细的研究，并建立了测定抗坏血酸的新方法。在优化的实验条件下，化学发光分析信号与抗坏血酸的浓度在1 x 10一几1 x 10礴mol/L之间呈线性关系。根据Iu队C规定，计算得该方法的检出限为5 x10一smol/L，对1 x10一smof几的抗坏血酸进行7次平行测量，相对标准偏差为0.8%。该方法已用于V。片剂中抗坏血酸含量的测定，结果令人满意。更多还原

【Abstract】 In general induction of this thesis, the history, the basic principles, characteristics and the main systems of chemiluminescence (CL) are briefly introduced and the applications of CL systems in pharmaceutical analysis in last ten years are intensively reviewed. In the research section, the new flow injection chemiluminescence(FI-CL) methods for the determination of menadione sodium bisulfite (MSB), dipyridamole(DIP), isoniazid and ascorbic acid have been developed.The goal of this thesis is to develop a series of new flow injection CL methods for the detection of Pharmaceuticals with highly sensitivity. The objective is to explore the pharmaceutical enhanced CL scheme of the follow-up CL reaction of luminol, which we found, and to develop the FI-CL methods for the determination of menadione sodium bisulfite (MSB), dipyridamole, isoniazid and ascorbic acid.CL analysis is becoming increasingly promising method for biomedical, environmental analysis owing to its simple instrumentation, high sensitivity, wide dynamic range, reproducibility, simplicity and rapidity. In recent years, various strategies for improving the selectivity of this method have been continued. Efforts to new CL reactions and this method coupled with the other analytic techniques make it very attractively.In the research section, a scheme of follow-up CL reaction of luminol was proposed. It is believed that the light-emitter is Aminophthalate, which was produced by the first CL reaction of luminol with an oxidant and its exciting energy transferred from the reaction of the oxidant with analyte pharmaceuticals.A novel and simple FI-CL method for the determination of MSB was developed based on the follow-up CL reaction of luminol with KIO4 We found that when menadione sodium bisulfite (MSB) was injected into a CL reaction-finished mixture of luminol and KIO4, a strong CL signal was produced. The analytical conditions including the length of the mixing tube and concentration of all reagents were optimized. Under the optimized condition, the CL signals responded linearly to the concentration of MSB from 2×10-9 g/mL to 4×10-5 g/mL with the detection limit of 8X 10-10 g/mL MSB. The relative standard deviation was less than 0.5% for 1×10-6g/mL MSB(n=ll). The developed method has been applied to determine MSB in the MSB injection samples with satisfactory results. Additionally, a scheme of follow-up CL reaction of luminol, in which lumiol was used as a CL precursor and KIO4 was used as an oxidant and analyte MSB was used as energy-transfer precursor, was proposed.A novel FI-CL method for the determination of dipyridamole(DIP) was developed based on the follow-up CL reaction of luminol with K3Fe(CN)6. When DIP was injected into a CL reaction-finished mixture of luminol and K3Fe(CN)6, a new CL reaction was initiated to produce strong CL emission. The CL intensity responded linearly to the concentration of DIP in the range from 1×10-10 to 4×10-7g/mL with a detection limit of 6×10-11 g/mL. The relative standard deviation was 1.1% for 1×10-8 g/mL DIP solution( n=7). The method has been applied to determine DIP in tablets and the results are in agreement with traditional method using UV spectrometry. Additionally, a scheme of follow-up CL reaction of luminol, in which luminol was used as a CL precursor and K3Fe(CN)6 was used as an oxidant and analyte MSB was used as energy-transfer precursor, was proposed.A simple FI-CL method for the determination of isoniazid was developed based on the follow-up CL reaction of luminol with KMnO4. It was found that a strong CL signal was produced when isoniazid was injected into a CL reaction-finished mixture of luminol and KMnCV Under the optimized condition, the CL signals responded linearly to the concentration of isoniazid from 5×10-8 g/mL to 1×10-4g/mL with a detection limit of 1×10-8g/mL. The relative standard deviation was 1.1% for 1×10-6 g/mL isoniazid (n=7). This method developed has been applied to determine isoniazid in tablets with satisfactory results. By the study of the CL spectrum, Fluo更多还原