基于毛细管电泳和离子迁移率经验公式测定洛伐他汀的绝对淌度和解离常数  

Determination of absolute mobility and dissociation constant of lovastatin using capillary electrophoresis and empirical equation of ion mobility

作　　者：罗芳 郭泽华 曹成喜 樊柳荫[3] 张薇[1] LUO Fang;GUO Zehua;CAO Chengxi;FAN Liuyin;ZHANG Wei(School of Life Science and Biotechnology, State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, China;School of Electronic Information & Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China;Student Innovation Center, Shanghai Jiao Tong University, Shanghai 200240, China)

机构地区：[1]上海交通大学生命科学技术学院,微生物代谢国家重点实验室,上海200240 [2]上海交通大学电子信息与电气工程学院,上海200240 [3]上海交通大学学生创新中心,上海200240

出　　处：《色谱》2021年第12期1362-1367,共6页Chinese Journal of Chromatography

基　　金：国家自然科学基金(22074091,21605101).

摘　　要：作为一种可以预防动脉粥样硬化和冠心病的潜在药物洛伐他汀,其绝对淌度m_(0)和解离常数pK_(a)值的测定有助于其性质与应用的研究。在前期相关研究基础上,该文提出了一种基于毛细管区带电泳(CZE)和离子淌度经验公式测定洛伐他汀m_(0)和pK_(a)的新方法。首先,根据经验公式由实际淌度(m_(act))、有效淌度(m_(eff))和m_(0)之间的关系推导出m_(0)的计算公式。对于一元酸HA,根据之前m_(0)的计算公式,以氢离子的浓度为自变量,m_(eff)的倒数为因变量可得到一条直线。根据这条直线的斜率计算得到pK_(a)。为了验证该方法的可行性和可靠性,应用该方法测定了巴比妥酸、苯甲酸、苄胺、苯酚、间甲酚等有机酸碱的m_(0)和pK_(a)值。同时,对于pH值低于6的缓冲体系,采用反向毛细管电泳技术,测定其pK_(a),并将测得的实验结果与理论参考值进行对比,发现两者具有较高的一致性,m_(0)的标准偏差小于6.0%,pK_(a)的标准偏差小于6.2%,且由线性回归方程的相关系数(R)可以看出测定pK_(a)时的线性回归直线拟合度较好,说明该文建立的新方法具有较高的可靠性。最后基于这种CZE与经验公式结合的新方法,采用二甲基亚砜(DMSO)作为电渗流标记物测定了洛伐他汀的m_(0)和pK_(a),得到的值分别为-1.70×10^(-8) m^(2)/(V·s)和9.00。该方法适用于酸性和碱性分析物m_(0)和pK_(a)等理化参数的测定,在药物分析尤其是新药理化特性研究中具有重要意义。In capillary electrophoresis,determination of the basic physical and chemical properties of compounds,such as absolute mobility(m_(0))and dissociation constant(pK_(a)),is of great practical significance.This is because the aforementioned properties are often used for the qualitative or quantitative analyses of the relevant compounds toward their application as potential drugs.Lovastatin is a potential drug candidate that can reduce the levels of cholesterol and low-density lipoprotein cholesterol in the blood,as well as prevent atherosclerosis and coronary heart disease.For a more convenient and rapid investigation of the properties and applications of lovastatin,it is necessary to determine its m_(0) and pK_(a) values.However,existing research on capillary electrophoresis for lovastatin and other related drugs focus on their quantitative determination,and their action mechanism and functions.Unfortunately,there are very few studies aimed at the determination of the m_(0) and pK_(a) values of lovastatin.Based on related studies,this paper herein proposed a novel method to determine m_(0) and pK_(a) of lovastatin.The present study mainly included a calculation method and experimental verification.The calculation method was based on capillary zone electrophoresis(CZE)and the empirical formula of ion mobility.First,on the basis of the empirical formula,the calculation formula for m_(0) was derived from the relationship between the actual mobility(m_(act)),effective mobility(m_(eff))and m_(0).Second,for a monovalent acid(HA),according to the calculation formula for m_(0) part,considering the hydrogen ion concentration as the independent variable and the reciprocal of m_(eff) as the dependent variable,a straight line was obtained on the coordinate axis.From the slope of this straight line,the dissociation equilibrium constant K_(a) was obtained directly,and pK_(a) was calculated easily.After the derivation of m_(0) and pK_(a) in the theoretical part,the feasibility and reliability of this method were verified by using

关 键 词：毛细管区带电泳 经验方程 淌度 解离常数 洛伐他汀 

分 类 号：O658[理学—分析化学]