注射用氨苄西林钠舒巴坦钠中有关物质HPLC检测方法的改进  

Improvement for determination of related substances concentration in ampicillin sodium/sulbactam sodium for injection

作　　者：姚蕾[1] 施亚琴[1] 胡昌勤[1] 

机构地区：[1]中国药品生物制品检定所抗生素室,北京100050

出　　处：《中国抗生素杂志》2009年第12期734-738,742,共6页Chinese Journal of Antibiotics

摘　　要：目的建立有效的注射用氨苄西林钠舒巴坦钠有关物质检测方法。方法采用HPLC梯度洗脱法,色谱柱为Phenomenex C18(2)型Luna色谱柱,以0.02mol/L磷酸二氢钠溶液pH(4.0±0.1)为流动相A、乙腈为流动相B;流速为1.0ml/min;检测波长为230nm和254nm,采用双波长检测分区域计算。对舒巴坦主峰前的杂质峰,采用230nm的峰面积值按舒巴坦计算其含量;对舒巴坦主峰后的杂质峰,采用254nm的峰面积值按氨苄西林计算其含量。结果采用梯度洗脱方式能有效检测出氨苄西林二聚物、舒巴坦青霉胺等杂质;不同来源的杂质具有明显分区,与氨苄西林有关的杂质主要集中在舒巴坦主峰后,而与舒巴坦有关的杂质则集中在舒巴坦主峰前;采用双波长分区域检测杂质含量,可以将复方制剂中的有关物质含量同其原料氨苄西林钠和舒巴坦钠中的有关物质含量相联系。各杂质在不同波长下响应值不同。结论改进后的方法可较好的分离氨苄西林钠和舒巴坦钠来源的各主要杂质,真实反映药品质量,有助于发现目前产品中的质量问题,进而促使产品质量的提高。Objective To development the method of separating and determining the related substances for injection of ampicillin sodium/sulbactam sodium. Methods HPLC gradient elution was performed by using Phenomenex C18 （2） colum, named Luna. The mobile phase was consisted of A, 0.02 mol/L phosphate buffer （pH4.0±0. 1 ）; and B, acetonitrile. The flow rate was 1. 0ml/min, the detection wavelength was 230nm/254nm. The concentration of related substances was quantified in different division by double wavelengths. The impurities of sulbactam, before the main peak of sulbactam, was quantified by external standard method of reference sulbactam in 230nm, and the impurities of ampicillin, after the main peak of sulbactam, was quantified by external standard method of reference ampicillin at 254nm. Results The isocratic elution method was available for detecting ampicillin dimer, （2S）-2-amino-3-methyl-3-sulphinobutanoic acid and other impurities. The impurities from different sources had obvious division, and the impurities of ampicillin mainly the peak of sulbactam, the impurities of sulbactam mainly before this peak. It was able to relate the result of related substances in the injection with the impurities in the single drug of ampicilln or suhactam, that detected in different division by double wavelengths. Conclusion The improved method can be used to separate the related substances from different components, and is suitable for controlling the quality of this drug.

关 键 词：氨苄西林钠舒巴坦钠复方制剂 有关物质 HPLC梯度洗脱法 质量标准 

分 类 号：R284.2[医药卫生—中药学] R978.11[医药卫生—中医学]