超高效液相色谱-质谱联用法研究阿洛西林的杂质谱  

UPLC/MS determination of the related substances of azlocillin for injection

作　　者：梁键谋 王志英 王悦 陈悦 LIANG Jian-mou;WANG Zhi-ying;WANG Yue;CHEN Yue(Zhejiang Institute for Food and Drug Control,Hangzhou 310052,China;Waters Technology Co.,Ltd.,Shanghai 201206,China)

机构地区：[1]浙江省食品药品检验研究院,杭州310052 [2]沃特世科技有限公司,上海201206

出　　处：《药物分析杂志》2020年第2期285-294,共10页Chinese Journal of Pharmaceutical Analysis

基　　金：浙江省药品监督管理局2020年度科技计划项目(2020014)。

摘　　要：目的:建立超高效液相色谱-质谱联用法检测注射用阿洛西林钠的有关物质,并建立杂质谱。方法:色谱柱为ACQUITY UPLC BEH C18(2.1 mm×100 mm,1.7μm);流动相A为10 mmol·L-1甲酸铵溶液(氨水调节pH至6.5),流动相B为乙腈-8 mmol·L-1甲酸铵溶液(4∶1);流速0.43 mL·min-1;柱温为40℃;检测波长为210 nm。结果:对市售的注射用阿洛西林钠进行检测,阿洛西林主峰与其相关物质峰分离良好,并对主要的、代表性的9个杂质进行了详细的鉴定解析。在所鉴定的杂质中,发现了在英国药典2000版阿洛西林钠各论收载的2个杂质,即阿洛西林青霉烯酸(为单个最大杂质),和其脱羧产生的杂质d以及4个聚合物杂质(包括二聚体)。结论:建立的超高效液相色谱-质谱联用法具有良好的分离能力,可用于定性分析,且阐明了注射用阿洛西林钠主药的裂解规律及其有关物质的裂解途径,为注射用阿洛西林钠的稳定性研究和杂质谱的研究提供了参考。Objective:To establish a suitable UPLC-MS method for the determination of the related substances of azlocillin for injection and the impurity spectrum.Methods:The HPLC method was applied with a octadecyl silane bonded silica gel(ACQUITY UPLC BEH C18,2.1 mm×100 mm,1.7μm)as a filler column;mobile phase A was 10 mmol·L-1 ammonium formate solution(adjust pH to 6.5 with ammonium hydroxide),mobile phase B was acetonitrile-8 mmol·L-1 ammonium formate solution(4∶1);the flow rate was 0.43 mL·min-1;the detection wavelength was 210 nm;the column temperature was 40℃.Results:Azlocilin and related substances were well separated.Under the positive ion mode,nine main impurities were separated from azlocillin components and identified on the basis of MS/MS spectra.And the impurities were analyzed in detail.Among the identified impurities,two impurities contained in the British Pharmacopoeia 2000 edition of aloxicillin sodium were found,namely,aloxicillin penicillienoic acid(the single largest impurity)and the impurity B generated by its decarboxylation,and four polymer impurities(including dimer)were also founded.Conclusion:Therefore,the method is rapid,sensitive and specific and it is suitable for determination of the related substances of azlocillin for injection.The proposed general fragmentation pathway of azlocillin is clarified and provides a reference for the impuritiy spectrum and the stability research of azlocillin sodium for injection.

关 键 词：超高效液相色谱-质谱联用法 注射用阿洛西林钠 有关物质 杂质谱 聚合物 

分 类 号：R917[医药卫生—药物分析学]