LC-MS/MS测定枸橼酸西地那非中磺酸酯类基因毒性杂质  

Determination of genotoxic impurity of suifonate ester in sildenafil citrate by LC-MS/MS

作　　者：李翠芬 李健华 陈新国 阮鹏伍 秦飞 LI Cuifen;LI Jianhua;CHEN Xinguo;RUAN Pengwu;QIN Fei(Guangzhou Baiyunshan Pharmaceutical Holdings Co.,Ltd.Baiyunshan Pharmaceutical General Factory,Guangzhou 510515,China;Key Laboratory of key Technology Research on Chemical Raw Materials and Preparations of Guangdong Province,Guangzhou 510515,China;Guangzhou Guobiao Inspection and Testing Co.,Ltd,Guangzhou 510535,China)

机构地区：[1]广州白云山医药集团股份有限公司白云山制药总厂,广州510515 [2]广东省化学药原料与制剂关键技术研究重点实验室,广州510515 [3]广州国标检验检测有限公司,广州510535

出　　处：《药学前沿》2024年第12期634-638,共5页China Pharmacist

基　　金：广州市科技计划项目(201906010026)。

摘　　要：目的建立液相色谱-串联质谱(LC-MS/MS)法测定枸橼酸西地那非中磺酸酯类基因杂质4-乙氧基-3-甲酰基-苯磺酸乙酯。方法色谱柱为Agilent Poroshell 120EC-C_(18)柱(150mm×2.1mm,2.7μm),柱温为25℃,流动相为0.1%甲酸溶液-甲醇,梯度洗脱,流速为0.3 mL/min,进样量为5μL。采用电喷雾离子源,以多反应监测模式进行正离子扫描,定量离子对为m/z 259.3→203.1,定性离子对为m/z 259.3→187.1。结果4-乙氧基-3-甲酰基-苯磺酸乙酯在4.92~196.99 ng/mL浓度范围内线性关系良好(r=0.9995),平均回收率为96.5%,RSD为4.2%(n=9),检测限为0.098 ng/mL,定量限为0.246 ng/mL。结论本方法操作简便、灵敏度高、结果可靠,可用于枸橼酸西地那非中4-乙氧基-3-甲酰基-苯磺酸乙酯的检测。Obiective To establish an liquid chromatography mass spectromete(LC-MS/MS)method for the determination of genotoxic impurity ethyl 4-ethoxy-3-formylbenzenesulfonate in sildenafil citrate.Methods The separation was carried out on Agilent Poroshell 120 EC-C_(18) column(150 mm×2.1 mm,2.7μm)at the column temperature of 25℃.The mobile phase was 0.1%formic acid solution-methanol with gradient elution,the flow rate was 0.3 mL/min and the injection volume was 5μL.The mass spectrometry was operated in electrospray ionization with multiplereactions monitoring mode.The quantitative ion pairs were m/z 259.3→203.1 and m/z 259.3→187.1.Results Ethyl 4-ethoxy-3-formylbenzenesulfonate had a good linear relationship within the concentration range of 4.92-196.99 ng/mL(r=0.9995).Its average recovery rate was 96.5%,and the RSD was 4.2%(n=9).The detection limit was 0.098 ng/mL and the quantification limit was 0.246 ng/mL.Conclusion The method is simple,sensitive and reliable,which can be applied to determine genotoxic impurity ethyl 4-ethoxy-3-formylbenzenesulfonate in sildenafil citrate.

关 键 词：枸橼酸西地那非 基因毒性杂质 磺酸酯 4-乙氧基-3-甲酰基-苯磺酸乙酯 高效液相色谱-串联质谱法 

分 类 号：R927.2[医药卫生—药学]