安美汀中高分子杂质的分离分析与质量控制

目的 :建立对安美汀 (阿莫西林 /克拉维酸钾 )中高分子杂质进行分离分析与质量控制的方法和指标。方法 :采用以SephadexG - 10 ,SephadexG - 15 ,TSK2 0 0 0SW ,TSK2 5 0 0PWXL等为填料的一系列凝胶色谱系统。结果 :确定了TSK2 5 0 0PWXL凝胶分离系统 ,采用对高分子杂质总量 (Kav <0 3)和分子量最大的杂质量 (Kav <0 1)进行联合控制的质控方法 ,其检测指标依据临床免皮试研究用样品的高分子杂质的检验结果而制订。结论 :方法简便 ,结果可靠 ,现已用于我国药品质量标准中对安美汀高分子杂质含量的控制。

Studies on the Separation and Quality Control of High Molecular Weight Impurities in Augmentin

Objective:To separate and determine the high molecular weight(HMW)impurities in augmentin(co-amoxicillin/clavulanic acid)and establish the method of quality control.Method:A series of gel filtration chromatography systems based on Sephadex G-10,Sephadex G-15,TSK 2000 SW,TSK 2500 PW XL .Results:The separation system of TSK 2500 PW XL gel filtration chromatography for HMW impurities in augmentin was developed.However,it was still difficult to identify each peak on chromatography due to heterogeneity of HMW polymer in augmentin.A lot of studies have shown that the more polymers exist the stronger allergenicity.So,it was suggested to control both total HMW polymers( K av<0 3) and the highest molecular weight polymer( K av<0 1)in augmentin.The limits of detection were set up according to the results of HMW polymers in the clinical samples exempt from the intradermal hypersensitive test studies.Conclusion:The method is simple ,rapid and reliable and accepted by the specification for controlling the quality of Augmentin.