胶束电动毛细管电泳法分析比阿培南中的有关物质

Analysis of Related Substances in Biapenam by Micellar Electrokinetic Capillary Chromatography

目的建立一种胶束电动毛细管电泳测定比阿培南中有关物质的分析方法。方法以含17 mmol·L^-13-(N,N-二甲基十六烷基铵)丙磺酸盐、3 mg·mL^-1月桂醇聚氧乙烯醚的90 mmol·L^-1三羟甲基氨基甲烷溶液(pH经H3PO4调节为2.5)为运行缓冲液,以内径50μm、长度48.5 cm的熔融石英毛细管为分离毛细管,分离电压22 kV,柱温30℃,进行了专属性、线性、检测限、精密度、重复性、稳定性等方法学考察实验,并将该方法应用于比阿培南原料药及制剂的检测中。结果本方法在缓冲液中加入两性离子电解质可以有效实现比阿培南与相邻杂质的分离,是液相色谱有力的补充分析方法。专属性实验表明,本方法尤其适合于比阿培南二聚物A、B及开环物的检测。结论本方法中将两性离子胶束电动毛细管电泳首次用于比阿培南(两性离子药物)的有关物质分析,灵敏度较高、专属性及重复性较好,为比阿培南的质量控制提供了一种可行的分析方法。

OBJECTIVE To establish a method for analysis of related substances in biapenem with micellar electrokinetic capillary chromatography(MEKC).METHODS In order to improve the separation selectivity,a zwitterionic surfactant,3-(N,N-dimethylhexadecylammonium)-propanesulfonate(PAPS)was used.The optimal separation conditions were as follows:the total length of the capillary was 48.5 cm(the effective length was 48 cm),the buffer was 90 mmol·L^-1 tris(hydroxymethyl)aminomethane(tris)-phosphate buffer containing 17 mmol·L^-1 PAPS and 3 mg·mL^-1 polyoxyethylene 23 lauryl ether(Brij 35),the applied voltage was 22 kV,and the capillary temperature was controlled at 30℃.Further more,the specificity,linearity,precision,repeatability,stability and durability were studied.The contents of related substances in biapenem commercial samples were analyzed.RESULTS The MEKC method,which was a comparable analysis method to HPLC,successfully separated the adjacent impurities of biapenem by using the zwitterionic surfactant PAPS.The specific test showed that this method was especially suitable for the detection of biapenem dimers A,B and open-ring compound.CONCLUSION In this method,MEKC with zwitterionic surfactant is for the first time applied to the analysis of related substances in biapenem(amphoteric drugs).It provides a feasible analysis method with high sensitivity,good specificity and reproducibility for the quality control of biapenem.