【作者】 赵文燕；

【导师】 陈安家；

【作者基本信息】 山西医科大学 ， 药学（专业学位）， 2016， 硕士

【摘要】 目的:金鸡纳生物碱(Cinchona ledgeriana(Howard)Moens ex Trim.)是喹啉衍生物,主要存在于金鸡纳树皮、茎皮和根皮中。金鸡纳树皮中含有三十多种生物碱,其中主要为奎宁(QN),其次为奎尼丁(QND)、辛可尼丁(CND)、辛可尼(CN)等,这四种生物碱占其质量的16%。QN主要用于疟疾的治疗,并有解热镇痛及局部麻醉的作用;此外它还能加强子宫收缩,可用于孕妇引产;另从茎皮和根皮中提取的生物碱QND可用于治疗心房颤动引起的阵发性心动过速和心房扑动等疾病。近年来,CN、CND及其衍生物常作为手性相转移催化剂被大量地应用到医药及化工领域。因此,有必要对金鸡纳生物碱的分离测定方法进行研究。QN、QND、CND、CN结构非常相似,其中QN和QND及CND和CN各有两个手性碳,互为非对映异构体,寻常方法很难对其拆分。本文采用毛细管电泳技术,应用不同类别的手性选择剂性试剂对四种生物碱进行了分离测定。方法:本文通过对毛细管电泳条件(手性选择剂的种类及浓度,缓冲溶液的种类﹑浓度和p H,电压,温度等)进行优化,确定了四种金鸡纳生物碱的分离和含量测定的最佳条件。结果:1.金鸡纳生物碱新型复合物的生成及其毛细管电泳分离条件:三(羟甲基)氨基甲烷18 mmol·L-1,醋酸铜3.0 mmol·L-1,羟丙基-β-环糊精20 mmol·L-1,电压20 k V,p H5.7。四种生物碱的出峰顺序依次为:辛可尼丁、奎宁、辛可宁、奎尼丁,其相应的分离度分别为5.66,3.94及9.08。2.配体交换毛细管电泳法分离四种金鸡纳生物碱的最佳的电泳条件为:手性选择剂L-赖氨酸4.0 mmol·L-1,醋酸铜2.0 mmol·L-1,缓冲溶液醋酸铵30 mmol·L-1,p H8.9,电压15 k V。金鸡纳生物碱的出峰顺序依次为:辛可宁、奎尼丁、辛可尼丁、奎宁,其相应的分离度分别为1.49,0.54及1.69。奎尼丁与辛可尼丁的分离度小于1.2,不能准确地直接进行面积积分,因此本实验应用一阶导数图谱进行面积积分。结论:上述两种分离方法都成功地应用于分离和测定一些实际样品诸如金鸡纳树皮,奎宁注射液,奎宁水及奎宁洗发水中四种生物碱的含量。更多还原

【Abstract】 Objective:Cinchona alkaloids(Cinchona ledgeriana(Howard) Moens ex Trim.) belongs to quinoline derivative, mainly in cinchona bark, bark and root bark. Cinchona tree bark contains over thirty alkaloids. The most abundant is quinine which together with quinidine,cinchonine, and cinchonidine, which can constitute up to 16% by mass of the cinchona tree bark. Quinine was used to treat malaria, and has antipyretic analgesic and local anesthetic effect. Furthermore, quinine was used to enhance uterine contractions so commonly used to induction. Quinidine which extract from the bark and root bark can be used for the treatment of atrial fibrillation, atrial flutter, paroxysmal tachycardia and other illnesses. In recent years, cinchonidine, cinchonine and its derivatives as chiral phase transfer catalyst were applied to the large field of medicine. So, it is necessary to study the technique in separation and determination of cinchona alkaloids.The structure of quinine, quinidine, cinchonidine and cinchonine are very similar,only two C chiral contrary, in which quinine, quinidine and cinchonidine, cinchonine are stereoisomers. Thus, it is difficult to separate. In this paper, two categories of chiral selectors were used to separation of two diastereomeric pairs of cinchona alkaloids(quinine/quinidine and cinchonine/cinchonidine) by capillary electrophoresis.Methods:In this paper, separation and determination of cinchona alkaloids parameters(such as chiral selector of the type and concentration of the buffer, p H and separation voltage) were investigated in order to achieve the optimum conditions.Results:Conditions of novel complex formation cinchona alkaloids were 18 mmol·L-1 tris(hydroxymethyl) aminomethane, 3.0 mmol·L-1 Cu(II) and 20 mmol·L-1 hydroxypr-opyl-β-cyclodextrin at p H5.7, and an applied voltage of 20 k V, of which four cinchona alkaloids migration order were cinchonidine, quinine, cinchonine, quinidine and the resolution were 5.66, 3.94 and 9.08 respectively.This article also applied ligand exchange capillary electrophoresis separated four cinchona alkaloids successfully. Optical resolutions of a single of cinchona alkaloids and of mixed cinchona alkaloids were obtained with 4.0 mmol·L-1 L-lys, 2.0 mmol·L-1 Cu(II)and 30 mmol·L-1 NH4 AC at p H8.9, and an applied voltage of 15 k V performed, of which four cinchona alkaloids migration order were cinchonine, quinidine, cinchonidine, quinine,and the resolution were 1.49, 0.54 and 1.69 respectively. Quinidine and cinchonidine could not be accurately to area of integral directly due to the resolution was less than 1.2.Therefore, the first derivative spectra were used to integrate the area.Conclusion:Both methods have been successfully applied to separation and determination of some real samples, such as cinchona bark quinine injection, quinine tonic water and shampoo.更多还原