柱切换LC-MSn法分析阿莫西林钠克拉维酸钾原料的杂质谱

Characterization of impurity profiles in co-amoxicillin and potassium clavulanate bulk material by online column-switching liquid chromatography tandem mass spectrometry

目的对阿莫西林钠克拉维酸钾复方原料中的杂质结构进行分析。方法采用BDS Hypersil C18色谱柱,以0.01mol/L磷酸二氢钾溶液(pH6.0)-乙腈为流动相进行梯度洗脱分离杂质;对阿莫西林钠克拉维酸钾(5:1)原料进行强力实验,归属杂质来源;采用柱切换-LC/MSn技术采集杂质的质谱数据,根据青霉素类抗生素的质谱裂解规律和降解反应机理,推定相关杂质的化学结构。结果在原料中共检出并推断出11种杂质的化学结构,均为阿莫西林相关杂质,未检出与克拉维酸钾相关的杂质。结论采用柱切换-LC-MSn技术可快速推定阿莫西林钠克拉维酸钾复方原料中相关杂质的化学结构,为《中国药典》中该类药品标准的提高提供了基础数据。

Objective To study the impurity structures in co-amoxicillin and potassium clavulanate bulk material. Methods Impurities in bulk material were eluted in gradients on a BDS Hypersil C18 column, with 0.01moL/L potassium dihydrogen phosphate （pH6）-acetonitrile as the mobile phase. Stress tests were designed and performed on the bulk material to specify those impurities. The impurities were analyzed by the application of the on-line column-switching LC-MSn method and their structures were characterized based on the degradation mechanism and the mass fragmentation regularity of penicillin. Results Eleven impurities were detected and characterized in the raw material. All of them were related to amoxicillin including seven degradation products and four derived impurities from synthesis process. Impurities related to potassium clavulanate were not detected. Conclusion This research can rapidly identify the structures of related impurities in co-amoxicillin and potassium clavulanate bulk material, and provide the basic data for the specification improvement of co-amoxicillin and potassium clavulanate product in China Pharmacopeia.