【作者】 王荣；

【导师】 马永钧；

【作者基本信息】 西北师范大学 ， 分析化学， 2020， 硕士

【摘要】 在本文中,以甲醛为主要衍生试剂对氨甲环酸和盐酸金刚烷胺两种胺类药物进行了柱前N-甲基化衍生反应,而衍生反应的产物与联吡啶钌试剂共存时能产生极强的电致化学发光信号,据此建立了用毛细管电泳-电致化学发光法分离分析这两种胺类药物的新方法。在电泳分析实验中,首次利用一种Mg²⁺-海藻糖-SiO₃^2-三元缔合物凝胶（MTS-gel）作为新型分离添加剂,极大地提高了毛细管电泳分离的效率。此外,在使用MTS-gel分离添加剂的前提条件下,以柱前N-甲基化衍生的氨基酸混合物标样为待测样,对单壁羟基碳纳米管/壳聚糖复合物内壁修饰毛细管分析柱的电泳分离能力进行了柱效评价实验。本论文主要研究内容如下:第一章:文献综述本章从毛细管电泳技术的发展状况、分离原理、分离添加剂等方面详细介绍了毛细管电泳技术的基础知识,重点介绍了毛细管电泳技术的几种主流检测方法;介绍了电化学发光分析当前的发展趋势,对电化学发光的基本类型进行了文献归纳和总结;简要介绍了毛细管电泳-电化学发光联用技术（CE-ECL）的概念和研究进展,并对其在分析领域中的应用实例作了文献综述。第二章:柱前衍生毛细管电泳-电致化学发光法测定日用化妆品中的氨甲环酸含量本章中将氨甲环酸进行N-甲基化衍生反应后,其衍生产物能与联吡啶钌电致化学发光试剂产生强的共发光信号,据此建立了毛细管电泳-电致化学发光法高选择性测定日用化妆品试样中氨甲环酸含量的新方法。实验中发现,添加一种Mg²⁺-海藻糖-SiO₃^2-三元缔合物凝胶至背景电解液中,可极大地改善电泳分离效能。在优化的分析条件下,氨甲环酸和内标物肌氨酸衍生产物的电泳峰可在500 s内达到完全分离,且此两个电泳峰的强度比值与氨甲环酸的初始浓度在10～750μmol/L的范围内呈良好的线性关系（相关系数R²=0.9993）,检出限为3.6μmol/L（S/N=3）。采用内标法对3种市售牙膏膏体和2种面膜护理液中的氨甲环酸进行了定量测定,测得这些试样中氨甲环酸含量的均值分别为4.05、0.24、6.06 mg/g和51.30、7.98mg/mL,加标回收率在92.5%～104.0%内,结果令人满意。第三章:用单壁羟基碳纳米管/壳聚糖内涂层分析柱毛细管电泳法测定药剂中的盐酸金刚烷胺含量本章用单壁羟基碳纳米管/壳聚糖内涂层修饰的毛细管为分离柱,以MTS-gel为分离添加剂的柱前衍生毛细管电泳-电致化学发光法（CE-ECL）对盐酸金刚烷胺进行了定量分析方法学研究。主要考察了柱前衍生盐酸金刚烷胺的关键反应条件、电泳测定条件和电致化学发光检测条件等因素的影响。在最优实验条件下,盐酸金刚烷胺衍生物和以固定浓度水平加入样品中内标肌氨酸衍生物的电泳峰间可在450 s内达到基线分离,且两个电泳峰的峰面积比值与盐酸金刚烷胺的初始浓度在10～250μmol/L和400～750μmol/L的范围内呈现出两段线性良好的定量关系曲线,其拟合方程分别为:A_AH/A_Sar=-0.1509+0.0942 C_AH,R²=0.9995;A_AH/A_Sar=-30.1729+0.1133 C_AH,R²=0.9991,检出下限为2.4μmol/L（S/N=3）。此外,对几种市售感冒药剂中的盐酸金刚烷胺进行了含量测定,实样加标回收率介于90.2%～102.9%之间,结果令人满意。第四章:几种纳米材料/壳聚糖内涂层分离柱毛细管电泳分离的柱效能评价以精氨酸、丙氨酸、甘氨酸、苯丙氨酸标样混合物作为测试样,用柱前衍生CE-ECL方法为实验技术手段,同时添加MTS-gel作为分离添加剂,考察了单壁羟基碳纳米管/壳聚糖内涂层分离柱对氨基酸混合物衍生样的电泳分离行为。此外,将MTS-gel凝胶中的Mg²⁺替换为同一主族的离子Ca²⁺和Sr²⁺时,合成出另两种同型三元缔合物凝胶,并对这三种凝胶的分离添加剂作用做了实验性对比性研究。由实验可知,使用单壁羟基碳纳米管/壳聚糖内涂层分离柱对混合氨基酸试样有良好的分离效能,而同时使用MTS-gel凝胶作分离添加剂时,对总分离效能呈现出明显的相互促进作用。更多还原

【Abstract】 In this thesis,because formaldehyde is used as a main N-methylation derivatization reagent for two amine drugs,tranexamic acid and amantadine hydrochloride,those reaction products can produce a very strong electrochemiluminescence signal when coexisting with tris（2,2’-bipyridine）ruthenium（II）.Based on this principle,a new method has established for the separation and analysis of two amine drugs by capillary electrophoresis coupled with chemiluminescence detection（CE-ECL）.In the electrophoretic analysis experiments,a ternary ionic association gel,Mg²⁺-trehalose-SiO₃^2-（MTS-gel）,has been used as a separation additive for the first time,which can greatly improves the electrophoretic separation efficiency.In addition,under the premise of using MTS-gel as the separation additive,when a mixture standard sample containing four amino acids is accepted to be the probe sample,the separation efficiency of the quartz capillary column coating with single-walled hydroxylation carbon nanotube/chitosan composite has been evaluated by pre-column derivatization CE-ECL method.The main research contents are as follows:Chapter one:The overview on this research fields is presented.In this chapter,the related knowledge of capillary electrophoresis technology,which includes the development trend,separation principle and separation additives about capillary electrophoresis technology,was introduced in detail.Especially,the several main detection methods that can be coupled to capillary electrophoresis are also reviewed.Additionally,the concept and principles of electrogenerated chemiluminescence and development of capillary electrophoresis coupled with electrochemiluminescence detection technique（CE-ECL）are briefly summarized,and some application examples of CE-ECL method in the field of analytical chemistry have been outlined.Chapter two:Determination of tranexamic acid content in essential cosmetics by pre-column derivatization capillary electrophoresis coupled with electrogenerated chemiluminescence detection.In this chapter,N-methylation of tranexamic acid yields an unique derivative,which generate strong co-luminescence signals in the presence of an electrochemiluminescence reagent such as Ru（bpy）₃²⁺.Using this principle,we established a highly selective analytical method based on pre-column derivatization capillary electrophoresis coupled with electrogenerated chemiluminescence detection for determining the tranexamic acid content in essential cosmetics.The addition of a ternary ionic association gel,Mg²⁺-trehalose-SiO₃^2-,in the components of background electrolyte greatly improved the electrophoretic separation efficiency.Under the optimized assay conditions,two electrophoretic peaks attributed to the derivatives of tranexamic acid and its internal standard（sarcosine）were completely separated in 500 s,and their electrophoretic peak intensities ratio showed a good linear relationship with the initial concentration of tranexamic acid in the range of 10-750μmol/L（correlation coefficient R²=0.9993）.The limit of detection was estimated to be 3.6μmol/L（S/N=3）.Moreover,the internal standard method was further applied to the quantitative determination of tranexamic acid content in three kinds of toothpaste and two kinds of nutrient solutions in facial masks.The results showed that the average tranexamic acid content in three toothpaste samples was 4.05,0.24,and 6.06 mg/g,while that in two facial masks was 51.30 and 7.98 mg/mL.The recoveries for the above-mentioned samples were within the range 92.5%to 104.0%,implying satisfactory results.Chapter three:Determination of amantadine hydrochloride in drug samples by capillary electrophoresis using a modified column coated with the single-walled hydroxylation carbon nanotube/chitosan composite.In this chapter,applied a modified quartz capillary coated with the single-walled hydroxylation carbon nanotube/chitosan composite as separation column and the MTS-gel as a separation additive,we had studied the quantitative assay methodology of amantadine hydrochloride by using pre-column derivatization capillary electrophoresis coupled with electrogenerated chemiluminescence detection（CE-ECL）.In the experiments,the many influencing factors that include the critical reaction conditions in pre-column derivatization process of amantadine hydrochloride,the working conditions of electrophoretic separations and detection parameters relating to the electrogenerated chemiluminescence signal were investigated.Under the optimal experimental conditions,the electrophoretic peaks of amantadine hydrochloride and the internal standard substance（sarcosine）added to the sample at a fixed concentration level could completely reach baseline separation within 450 s,and their peaks area ratio(A_AH/A_Sar)showed a good linear relationship to the initial concentration value of amantadine hydrochloride in the two segment range of 10-250μmol/L(A_AH/A_Sar=-0.1509+0.0942C_AH,R²=0.9995)and 400-750μmol/L(A_AH/A_Sar=-30.1729+0.1133 C_AH,R²=0.9991),respectively.The detection limit was also estimated to be 2.4μmol/L（S/N=3）.In addition,the new analytical method had been applied to the determination of amantadine hydrochloride content in several anti-cold medicaments.The recoveries for the real samples were between 90.2%and 102.9%,and the results were satisfactory.Chapter four:Evaluation of electrophoretic separation efficiency of modified quartz capillaries coated with several nano-materials/chitosan composite.In this chapter,with a mixed standard amino acid sample containing arginine,alanine,glycine and phenylalanine as an indicating sample and the ternary ionic association gel（MTS-gel）as the separation additive,we investigated the electrophoretic separation behavior of an indicating sample by pre-column derivatization CE-ECL method.When Mg²⁺ion in the the process of synthesis reaction of MTS-gel was replaced Ca²⁺and Sr²⁺belonging to the same main group of elements,the two ternary ionic association gels had also been synthesized as the separation additives,and their action contributing to the electrophoretic separation efficiency of a mixed standard amino acid sample had been comparatively studied.From experimental results,the four amino acid derivatives in the indicating sample could be effectively separated by the modified quartz capillary column coated with the single-walled hydroxylation carbon nanotube/chitosan composite.In particular,when using the MTS-gel gel as a separation additive simultaneously,the total separation efficiency of electrophoretic separation for a mixed standard amino acid sample would be significantly enhanced by the mutual promotion mode.更多还原