【作者】 何聿；

【导师】 张兰；

【作者基本信息】 福州大学 ， 分析化学， 2005， 硕士

【摘要】 肿瘤特别是恶性肿瘤是对人类健康威胁最严重的疾病之一。本论文选择了分析化学研究热点毛细管电泳法,兼容了分离科学和生命科学等领域的前沿课题作为研究内容,对一些肿瘤标记物及抗癌药物进行了系统的理论分析及应用研究。首先,对肿瘤的产生、诊断、治疗以及抗肿瘤药物的基本情况作了概述,指出毛细管电泳在核酸与药物分析方面的优势,提出本论文所要从事的研究工作的设想。应用CV、LSV 和DPV 等电化学方法对7-甲基鸟苷在玻碳电极上的伏安行为进行了研究,讨论了电极反应过程及机理,为毛细管电泳与电化学检测法联用提供了电化学研究基础。并建立了微分脉冲伏安法快速测定7-甲基鸟苷的电化学方法。该法选择性好、操作简单、快速、准确可靠,结果令人满意。用自组装的毛细管电泳-安培检测装置对肿瘤标记物7-甲基鸟苷和抗肿瘤抗生素丝裂霉素进行分离检测,旨以修饰核苷的含量表征临床抗肿瘤药物的疗效。7-甲基鸟苷与丝裂霉素C 检测限分别为0.050 μg/mL 与0.025 μg/mL,对模拟样品的测定获得良好的结果。本方法操作简单、无需对样品进行前处理、重现性好。由于抗肿瘤药物多具有骨髓毒性,为了考察其对人体的损害,采用毛细管电泳-安培检测法对修饰核苷(1-甲基鸟苷)、正常核苷(鸟苷)和两种抗肿瘤药物(丝裂霉素、5-氟尿嘧啶)进行了考察。在最优条件下,四组分在8 min 内实现基线分离,并成功用于模拟生物试样中上述四组分测定。针对肿瘤临床治疗中采用的多药联合化疗的实际用药情况,应用毛细管电泳-紫外检测法建立一种简单、快速用于7 种包含合成和天然抗肿瘤药物的定量分析方法。研究了毛细管区带电泳分离的主要因素,得到最优分离条件。该法成功地用于模拟尿样及模拟血浆中各组分的测定,回收率范围介于90.0~109.2%,可作为快速测定体内抗肿瘤药物的新方法。最后,结合课题项目对抗精神病药物奋乃静与氟奋乃静的CZE-柱端安培检测法进行了研究。并将该法用于实际药物片剂中奋乃静与氟奋乃静浓度的测定,结果令人满意。更多还原

【Abstract】 Tumor, especially malignant tumor is one of the gravest threats to human beings. In this thesis, as a hot spot of analytical chemistry, capillary electrophoresis was chosen to study the tumor markers and some anticarcinogens. In part 1, the general situation of tumor markers and the progress of determination method and nucleotide were reviewed. In part 2, some modern electrochemical techniques, such as LSV, CV and DPV were used for researching the behavior of 7-methylguanosine. It provided the foundation for the following study by capillary electrophoresis with amperometric detection (CZE-AD). Their electrochemical characteristics at the surface of glassy carbon electrode have also been studied. The method was applied to the assay of 7-methylguanosine in imitative human serum and urine with satisfactory results. To investigate the curative effect of anticarcinogens, a simple, quick and sensitive method was employed for determination of 7-methylguanosine and Mitomycin by CZE-AD (in part 3). Under the optimum conditions, the current response was liner over about two orders of magnitude with detection limits (S/N =3) 0.050 and 0.025 μg/mL for 7-Methlguanosine and Mitomycine C. With the purpose of studying the toxicity of anticancer drugs that will inflict damage to human being, in part 4, a CZE-AD method was developed and applied for the separation and determination of Mitomycin, Fluoroplex, 1-Methylguanosine and Guanosine simultaneously. The conditions for separation and detection of a mixture of four analytes have been optimized, and the results showed that the investigated compounds could be successfully separated within 8 min. The method has been employed for the determination of Mitomycin, Fluoroplex, 1-Methylguanosine and Guanosine in imitative human serum, urine and plasma. Aim at the fact that combined treatment is widely used in the field of clinic. In part 5, the seven anticarcinogens were studied by used capillary electrophoresis with UV detection. Under the optimal condition, the seven anticarcinogens were baseline separated in 20 mmol/L borate buffer at pH 9.2, in less than 9 min. The proposed method has been successfully applied to analyze the imitative urine and plasma samples with satisfactory assay results. The recoveries were found to be in the range of 90.0~109.2%. In part 6, Perphenazine and Fluphenazine are determinated using CZE/end-column amperometric detection. The proposed method has been successfully applied to determine the content of Perphenazine and Fluphenazine in Perphenazine tablet, Fluphenazine tablet with satisfactory results.更多还原