Ishihama Y, Oda Y, Asakawa N
Department of Physical and Analytical Chemistry, Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
J Pharm Sci. 1994 Oct;83(10):1500-7. doi: 10.1002/jps.2600831025.
Dissociation constants (pKaS) of acidic, basic, and amphoteric pharmaceuticals were exactly determined by capillary electrophoresis. A general equation for use in calculation of pKaS from solute mobilities observed at different pHs was derived to be suitable for a multivalent compound with close pKaS such as angiotensins, which are bioactive octa- or decapeptides. The obtained pKa values were highly consistent with the values determined by conventional methods. For verapamil, the detection limit was 9.8 microM (49 fmol), the total analysis time was 12 min, and the relative standard deviation of the obtained pKa value was 0.11%. This method was also applicable to a mixture of two components, e.g., a bioactive compound and the prodrug, because they have different mobilities and are separated from each other.
通过毛细管电泳精确测定了酸性、碱性和两性药物的解离常数（pKa）。推导了一个通用方程，用于根据在不同pH值下观察到的溶质迁移率计算pKa，该方程适用于具有相近pKa的多价化合物，如血管紧张素，血管紧张素是具有生物活性的八肽或十肽。所获得的pKa值与通过传统方法测定的值高度一致。对于维拉帕米，检测限为9.8微摩尔（49飞摩尔），总分析时间为12分钟，所获得的pKa值的相对标准偏差为0.11%。该方法也适用于两种成分的混合物，例如生物活性化合物和前药，因为它们具有不同的迁移率且彼此分离。
