本文選題：化學(xué)計(jì)量學(xué) + 多維校正��； 參考：《湖南大學(xué)》2016年碩士論文

【摘要】：近年來(lái),基于多線性成分的多維校正方法受到了分析化學(xué)者越來(lái)越多的關(guān)注,借助于“數(shù)學(xué)分離”輔助或代替?zhèn)鹘y(tǒng)的物理化學(xué)分離,可以實(shí)現(xiàn)在未知干擾共存下感興趣組分的定量分析�；瘜W(xué)計(jì)量學(xué)中的“二階優(yōu)勢(shì)”為多個(gè)目標(biāo)分析物的同時(shí)定量提供了新思路。隨著分析儀器以及計(jì)算機(jī)的快速發(fā)展,化學(xué)計(jì)量學(xué)二階校正方法結(jié)合不同儀器產(chǎn)生的復(fù)雜數(shù)據(jù),可用于不同復(fù)雜背景如藥物、食品、化妝品以及環(huán)境樣中感興趣組分的定量分析,尤其是動(dòng)態(tài)體系下感興趣組分的定量。目前,許多重大疾病(如癌癥、心血管病以及風(fēng)濕病)治療的優(yōu)化尤為重要。因此,本文作者在了解多維校正理論知識(shí)基礎(chǔ)上,將多維校正方法結(jié)合不同的儀器分析用于復(fù)雜體系中不同藥物和生物大分子的定量分析,并進(jìn)一步探索了普魯卡因與人血清白蛋白相互作用的機(jī)理。主要內(nèi)容如下：第二章：二階校正輔助的HPLC-DAD方法用于快速定量人體血漿中四種酪氨酸激酶抑制劑酪氨酸激酶是細(xì)胞生長(zhǎng)和分化中至關(guān)重要的調(diào)節(jié)因子。在許多重大疾病如風(fēng)濕性關(guān)節(jié)炎和癌癥中,均發(fā)現(xiàn)其激酶信號(hào)調(diào)節(jié)異常。研究發(fā)現(xiàn),酪氨酸酶介導(dǎo)的信號(hào)轉(zhuǎn)導(dǎo)與腫瘤的發(fā)生和惡化密切相關(guān)。因此,通過(guò)阻斷激酶信號(hào)傳導(dǎo)通路可以有效治療該類(lèi)疾病。凡德他尼、帕唑帕尼、阿法替尼和達(dá)沙替尼是四種不同的酪氨酸激酶抑制劑,已被批準(zhǔn)用于甲狀腺髓樣癌、腎癌、白血病等的治療。本章利用交替三線性分解(ATLD)結(jié)合高效液相色譜二極管陣列檢測(cè)(HPLC-DAD)方法用于同時(shí)定量分析7種不同人體血漿樣中凡德他尼、帕唑帕尼、阿法替尼和達(dá)沙替尼的含量,發(fā)展了一種快速、靈敏、有效的抗癌藥物定量方法。第三章：二階校正方法結(jié)合HPLC-DAD定量分析人體體液中三種抗凝藥物和利伐沙班片中的活性物質(zhì)本章采用HPLC-DAD結(jié)合ATLD二階校正方法用于定量分析血漿樣和尿液樣中的利伐沙班、阿哌沙班和達(dá)比加群酯的濃度,并準(zhǔn)確定量了利伐沙班片中利伐沙班的實(shí)際含量。利伐沙班、阿哌沙班和達(dá)比加群酯是新型口服抗凝藥,相對(duì)于傳統(tǒng)的抗凝藥物如肝素和低分子肝素、水蛭素、重組水蛭素、阿加曲班和西美加群以及維生素K拮抗劑華法林等,新型抗凝藥物不易受食物、藥物等影響。本章提出的方法簡(jiǎn)單、經(jīng)濟(jì)、省時(shí)、省力,且具有較好的準(zhǔn)確性和重復(fù)性,可用于常規(guī)的利伐沙班質(zhì)量控制,有望發(fā)展成為一種沙班類(lèi)藥物實(shí)時(shí)的血藥濃度的監(jiān)測(cè)方法。第四章：內(nèi)源熒光結(jié)合二階校正方法用于快速定量分析復(fù)雜基質(zhì)中吲哚美辛含量吲哚美辛,是一種非甾體抗炎藥,通過(guò)抑制環(huán)氧酶的合成減少前列腺素的生成,從而具有解熱、鎮(zhèn)痛和抗炎功效。本章采用三維熒光結(jié)合平行因子分析(PARAFAC)算法策略,實(shí)現(xiàn)了人體血漿樣、尿液樣以及吲哚美辛腸溶片中活性成分的定量分析。即使背景干擾與待分析物的熒光光譜嚴(yán)重重疊,采用化學(xué)計(jì)量學(xué)的“數(shù)學(xué)分離”代替?zhèn)鹘y(tǒng)的物理化學(xué)分離,實(shí)現(xiàn)了感興趣組分有效定量信息的提取。實(shí)驗(yàn)過(guò)程簡(jiǎn)單、快速,可避免復(fù)雜的樣本預(yù)處理,提高了分析結(jié)果的準(zhǔn)確性。第五章：多維校正方法結(jié)合三維血清白蛋白(HSA)作為人體內(nèi)循環(huán)系統(tǒng)中一種常見(jiàn)的可溶性蛋白質(zhì),扮演著重要的生化角色,通過(guò)研究藥物小分子與血清白蛋白的相互作用機(jī)理,有助于了解藥物的吸收、分布、代謝和排泄。通常情況下,弱結(jié)合力使得血漿中游離的藥物濃度較高,藥物可以快速發(fā)揮其藥效：強(qiáng)的作用力則導(dǎo)致藥物的血藥濃度較低,從而導(dǎo)致藥物作用時(shí)間長(zhǎng),代謝慢。這種行為與不同的藥物的化學(xué)結(jié)構(gòu)以及給藥方式有關(guān)。因此,研究藥物與HSA的結(jié)合機(jī)理對(duì)藥物劑型開(kāi)發(fā)以及藥物的藥效學(xué)具有重要意義。本章提出一種三維熒光結(jié)合二階校正方法用于HSA與普魯卡因(PRO)動(dòng)態(tài)體系中游離HSA濃度的定量分析,并利用三階校正方法探索了溫度對(duì)HSA和PRO相互作用的影響。
[Abstract]:In recent years, multidimensional correction based on multilinear components has attracted more and more attention from analytical chemistry. By means of "mathematical separation" assisting or replacing traditional physical and chemical separation, the quantitative analysis of interesting components can be realized under the coexistence of unknown interference. The "two order advantage" in stoichiometry is a multiple target analysis. With the rapid development of analytical instruments and computers, the two order correction method of chemometrics, combined with complex data produced by different instruments, can be used for quantitative analysis of interesting components in different complex backgrounds, such as drugs, food, cosmetics and environmental samples, especially in dynamic systems. At present, the optimization of the treatment of many major diseases, such as cancer, cardiovascular disease and rheumatism, is particularly important. Therefore, on the basis of knowledge of the theory of multidimensional correction, the author combines the multidimensional correction method with different instruments to analyze the quantitative analysis of different drugs and biological macromolecules in the complex system, and further explores it. The mechanism of the interaction of procaine and human serum albumin. The main contents are as follows: the second chapter: the two order correction assisted HPLC-DAD method is used for the rapid quantitative determination of four tyrosine kinase inhibitors tyrosine kinase in human plasma, which is the key regulator of cell growth and differentiation. In many major diseases such as rheumatic joints It is found that tyrosinase mediated signal transduction is closely related to the occurrence and deterioration of the tumor. Therefore, this type of disease can be effectively treated by blocking the kinase signal transduction pathway. Van derani, palazolani, alafinib and dasatinib are four different tyrosine kinases Inhibitors have been approved for the treatment of medullary thyroid carcinoma, kidney cancer, and leukemia. This chapter uses the alternating three linear decomposition (ATLD) combined with high performance liquid chromatography diode array detection (HPLC-DAD) method for the simultaneous quantitative analysis of the contents of van der tadoni, parazazoli, alafinii and dasatinib in 7 different human plasma samples. A rapid, sensitive and effective quantitative method for anticancer drugs. The third chapter: the two order correction method combined with HPLC-DAD for quantitative analysis of three anticoagulants in human body fluid and the active substance in Rivaroxaban tablets. This chapter uses HPLC-DAD combined with ATLD two order correction method for quantitative analysis of lefal Shaaban and artha in blood samples and urine samples. The concentration of the class and dabiaga group and accurate quantitative determination of the actual content of lefal Shaaban in Rivaroxaban tablets. Lev Shaaban, ABO Shaaban and dabiaga are new oral anticoagulants, relative to the traditional anticoagulants such as heparin and low molecular weight heparin, hirudin, recombinant hirudin, acataban and simeg group, and vitamin K antagonists. Hua Falin and so on, the new anticoagulant drugs are not easy to be affected by food and medicine. The method proposed in this chapter is simple, economical, time-saving, laborsaving, and has good accuracy and repeatability. It can be used for the conventional Lev Shaaban quality control. It is expected to develop into a method of monitoring the concentration of blood drugs in the real time of Shaaban drugs. The fourth chapter: endogenous fluorescent junction The combined two order correction method is used for the rapid quantitative analysis of indomethacin in complex matrix. It is a nonsteroidal anti-inflammatory drug, which reduces the production of prostaglandins by inhibiting the synthesis of epoxide, and thus has antipyretic, analgesic and anti-inflammatory effects. This chapter uses a three dimensional fluorescence binding parallel factor analysis (PARAFAC) algorithm. The quantitative analysis of the active components in human plasma, urine and Indometacin Enteric-coated Tablets. Even if the background interference and the fluorescence spectrum of the analyte are seriously overlapped, the chemometrics "mathematical separation" is used instead of the traditional physical and chemical separation to achieve the extraction of effective quantitative information of the interesting components. The experimental process is simple and rapid. It can avoid complex sample pretreatment and improve the accuracy of analysis results. The fifth chapter: multidimensional correction method combined with three dimensional serum albumin (HSA) as a common soluble protein in the internal circulation system, plays an important biochemical role, and helps to study the interaction mechanism between small drug molecules and serum albumin. To understand the absorption, distribution, metabolism, and excretion of drugs. Generally, the weak junction force makes the concentration of free drugs in the plasma higher, and the drug can give full play to its efficacy: the strong force leads to the lower concentration of the drug, which leads to the long time and slow metabolism of the drug. This behavior and the chemical structure of different drugs It is of great significance to study the mechanism of combination of drugs and HSA for the development of drug dosage forms and pharmacodynamics. In this chapter, a three-dimensional fluorescence combined two order correction method is proposed for quantitative analysis of free HSA concentration in the dynamic system of HSA and procaine (PRO), and the temperature is explored by using the three order correction method. The effect on the interaction of HSA and PRO.
【學(xué)位授予單位】：湖南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R917
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本文編號(hào)：2064946