注射用磺苄西林钠的杂质谱研究  

Analysis of Impurity Profile of Sulbenicillin Sodium for Injection

作　　者：潘芳芳 何佳佳 罗英 陈悦 PAN Fang-fang;HE Jia-jia;LUO Ying;CHEN Yue(Zhejiang Instituie for Food and Drug Control,Hangzhou,310052,China)

机构地区：[1]浙江省食品药品检验研究院,杭州310052

出　　处：《中国药学杂志》2020年第22期1883-1889,共7页Chinese Pharmaceutical Journal

摘　　要：目的建立高效液相色谱串联高分辨质谱检测器的方法,研究注射用磺苄西林钠的杂质谱并进行来源归属。方法采用Agilent 1290 HPLC-6538 Q-TOF高效液相色谱质谱联用仪,流动相为10 mmol·L^(-1)甲酸铵溶液-8 mmol·L^(-1)甲酸铵溶液(体积分数80%乙腈溶液作溶剂)=87∶13;色谱柱为Ultimate XB C_(18)(4.6 mm×250 mm,5μm);流速1.0 mL·min^(-1);质谱检测器采用电喷雾离子源(ESI),负离子扫描模式;数据采集范围m/z 50~1 000,离子源前进样分流比2∶1,毛细管电压3.5 kV,锥孔电压65 V,喷雾气压310 kPa,干燥气(氮气)流量12 L·min^(-1),干燥气温度325℃,碎裂电压150 V。通过分析主成分与未知杂质多级质谱行为的相关性以及主成分的合成工艺推定其结构。结果将5个厂家样品中的主要杂质归纳为14个未知杂质,解析其质谱碎片进行结构推测和来源归属。结论研究结果对注射用磺苄西林钠的质量控制和工艺评价具有指导意义。OBJECTIVE To establish an HPLC-MS method for analysis of the impurity profile of sulbenicillin sodium for injection and confirm their coming source.METHODS Agilent 1290 HPLC-6538 Q-TOF was used,and the column was Ultimate XB C18(4.6 mm×250 mm,5μm).The mobile phase was 10 mmol·L-1 ammonium formate and 8 mmol·L-1 ammonium formate(solvent was 80%acetonitrile solution)(87∶13).The flow rate was 1.0 mL·min-1.ESI source was used.Negative ion scan was conducted with a scanning range of m/z 50-1000.Post-column diversion ratio was 1∶2.Then capillary voltage was 3.5 kV and taper hole voltage was 65 V.The nebulizing pressure was 310 kPa and dry gas(N2)flow was 12 L·min-1.The dry gas temperature was 325℃.The cataclastic voltage was 150 V.Then the unknown impurities were deduced by comparing the similarities and difference with sulbenicillin in mass spectrum as well as the production process.RESULTS Fourteen related substance were separated and detected in the samples from five manufacturers.Their structures were identified by analyzing their fragmentation pathway in MS.And the sources were determined.CONCLUSION The method is helpful for the quality control of sulbenicillin sodium for injection and optimization of the synthetic process.

关 键 词：磺苄西林钠 有关物质 杂质谱 三重四极杆飞行时间质谱 

分 类 号：R917[医药卫生—药物分析学]