| 张静姝,颜梦梦,刘春叶.化学通报,2016,79(12):1166-1172. |
| 毛细管电泳-内标法同时测定3种药物的解离常数 |
| Simultaneous Determination of Dissociation Constants of Three Drugs by Internal Standard Capillary Electrophoresis |
| 投稿时间：2016-06-21 修订日期：2016-07-13 |
| DOI： |
| 中文关键词: 毛细管电泳 内标 解离常数 |
| 英文关键词:Capillary electrophoresis, Internal standard, Dissociation constant |
| 基金项目:陕西科技计划项目农业攻关项目 |
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| 中文摘要: |
| 本文采用毛细管电泳-内标法对普萘洛尔、阿替洛尔和美托洛尔等3种一元弱碱性药物的解离常数同时进行测定。选取麻黄碱、普鲁卡因和苯海拉明等3种物质为内标物，应用毛细管电泳-内标法及迭代计算法确定内标物的解离常数。测定内标物和分析物在部分和完全质子化条件下的有效电泳淌度，通过单内标体系和多内标体系对3种分析物的解离常数同时进行测定，并对方法的精密度和准确度进行考察。实验结果的相对标准偏差为0.26%～0.96%，测定值与相同条件下单组分测定结果及文献值相差均小于0.1个pKa单位。该方法不需准确测定缓冲溶液的pH，仅需2次电泳分析即可同时测得3种药物的解离常数，显著缩短了分析时间，适用于高通量的药物评估及筛选。 |
| 英文摘要: |
| Simultaneous determination of dissociation constants of three monoprotic weak base drugs, propranolol, atenolol and metoprolol were achieved through internal standard capillary electrophoresis. Three compounds that have similar properties and dissociation constants with the analytes, ephedrine, procaine and diphenhydramine were selected as the internal standards. Precise dissociation constants of the internal standards were deduced using iterative calculation by internal standard capillary electrophoresis. Effective electrophoretic mobilities of the internal standards and the analytes have been determined under the conditions that they are partly or totally protonated. Dissociation constants of the three analytes were further determined simultaneously through single internal standard and multi-internal standards systems, the precision and accuracy of the method were investigated. The relative standard deviation of experimental results were in the range of 0.26%～0.96%, and the obtained values were accurate within 0.1 pKa unit compared with results of monocomponent determination under the same conditions and the literature values. The technology did not require accurate pH measurement of the buffer solution. Only two electrophoretic runs are needed to complete simultaneous determination of dissociation constants of the three drugs, so the consumed experiment time is shortened significantly. Therefore the proposed method is highly appropriate for high throughput evaluation and screening of drugs in drug development process. |
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