Hansen Steen Honoré, Sheribah Zeinab Awad
Department of Analytical Chemistry, The Danish University of Pharmaceutical Sciences, Copenhagen.
J Pharm Biomed Anal. 2005 Sep 1;39(1-2):322-7. doi: 10.1016/j.jpba.2005.03.017.
The purpose of the present investigation was to develop a test for related substances in the benzodiazepine drug substance bromazepam based on capillary electrophoresis (CE). A final method for the determination of impurities in bromazepam is based on non-aqueous capillary electrophoresis (NACE). Five modes of capillary electrophoresis were investigated and compared for the said purpose. All the CE systems investigated make use of running buffers at low pH in order to protonate the analytes. A low pH of the running buffers was needed as the pK(a) values of benzodiazepines in general are in the range from 1.3 to 4.6. Dynamically coated capillaries were used to overcome the low electro-osmotic flow at low pH in the aqueous buffers investigated. CZE with and without dynamical coating of the internal surface of the fused capillaries was compared and also micellar electrokinetic chromatography (MEKC) as well as microemulsion electrokinetic chromatography (MEEKC) performed in dynamically coated capillaries were investigated. The NACE was chosen as the best technique as the low solubility of the benzodiazepines in water is easily overcome. The NACE system showed good selectivity and detectability for the substances investigated and the limit of quantitation for the impurities corresponded to 0.05% of the drug substance. Linearity was good.
本研究的目的是开发一种基于毛细管电泳（CE）的苯二氮䓬原料药溴西泮中有关物质的检测方法。溴西泮中杂质测定的最终方法基于非水毛细管电泳（NACE）。为实现该目的，研究并比较了五种毛细管电泳模式。所有研究的CE系统均使用低pH运行缓冲液以使分析物质子化。由于苯二氮䓬类药物的pK(a)值一般在1.3至4.6范围内，因此需要低pH的运行缓冲液。使用动态涂层毛细管来克服所研究的水性缓冲液在低pH下低的电渗流。比较了有和没有对熔融毛细管内表面进行动态涂层的毛细管区带电泳（CZE），还研究了在动态涂层毛细管中进行的胶束电动色谱（MEKC）以及微乳液电动色谱（MEEKC）。由于苯二氮䓬类药物在水中的低溶解度很容易被克服，因此选择NACE作为最佳技术。NACE系统对所研究的物质显示出良好的选择性和检测能力，杂质的定量限相当于原料药的0.05%。线性良好。
