UPLC-MS/MS法同时检测丁二磺酸腺苷蛋氨酸肠溶片中3种1,4-丁二磺酸酯类基因毒性杂质  

Simultaneous detection of three 1,4-butanedisulfonate genotoxic impurities in ademetionine butanedisulfonate enteric coated tablets by UPLC-MS/MS

作　　者：覃玉梅 袁铭铭 和燕玲 叶继威 李春燕 周雪飞 吴春艳 段光玉 邵伍军 QIN Yumei;YUAN Mingming;HE Yanling;YE Jiwei;LI Chunyan;ZHOU Xuefei;WU Chunyan;DUAN Guangyu;SHAO Wujun(Zhejiang Haizheng Pharmaceutical Co.,LTD.,Taizhou Zhejiang 318000,China;Jiangxi Institute for Drug Control,Nanchang Jiangxi 330029,China;Taizhou Vocational College of Science&Technology,Taizhou Zhejiang 318000,China)

机构地区：[1]浙江海正药业股份有限公司,浙江台州318000 [2]江西省药品检验检测研究院,江西南昌330029 [3]台州科技职业学院,浙江台州318000

出　　处：《中兽医医药杂志》2023年第3期22-27,共6页Journal of Traditional Chinese Veterinary Medicine

基　　金：江西省药品监督管理局科研项目(2019JS17);台州市科学技术局(21nya10)。

摘　　要：建立丁二磺酸腺苷蛋氨酸肠溶片中3种1,4-丁二磺酸酯类基因毒性杂质(1,4-丁二磺酸二甲酯、1,4-丁二磺酸二乙酯和1,4-丁二磺酸二异丙酯)的超高效液相色谱-三重四级杆质谱(UPLC-MS/MS)检测方法。采用Agilent Poroshell 120 PFP色谱柱(3.0 mm×150.0 mm,2.7μm),以0.01 mol/L甲酸铵(A)-甲醇(B)为流动相,流速为0.4 mL/min,进行梯度洗脱。采用质谱检测器,在电离模式ESI+、多反应监测(MRM)模式下采集数据。结果显示,1,4-丁二磺酸二甲酯、1,4-丁二磺酸二乙酯和1,4-丁二磺酸二异丙酯分别在0.999 6~19.992 0 ng/mL、0.997 2~19.944 0 ng/mL、0.996 8~19.936 0 ng/mL范围内线性关系良好,相关系数r均为1.000 0,定量限浓度分别为0.999 6 ng/mL、0.997 2 ng/mL、0.996 8 ng/mL,检测限浓度分别为0.299 9 ng/mL、0.299 2 ng/mL、0.299 0 ng/mL,样品加标回收率均为80%~120%。该方法可以快速、简便、灵敏、准确地测定丁二磺酸腺苷蛋氨酸肠溶片中1,4-丁二磺酸二甲酯、1,4-丁二磺酸二乙酯和1,4-丁二磺酸二异丙酯的含量,为丁二磺酸腺苷蛋氨酸肠溶片的质量控制提供参考依据。A UPLC-MS/MS method was established for simultaneous determination of three 1,4-butanedisulfonate genotoxic impurities in ademetionine butanedisulfonate enteric coated tablets:Dimethyl 1,4-butanedisulfonate,diethyl1,4-butanedisulfonate,and diisopropyl 1,4-butanedisulfonate.The Agilent Poroshell 120 PFP chromatographic column(3.0 mm×150.0 mm,2.7 μm) was used for gradient elution with 0.01 mol/L ammonium formate as mobile phase A and methanol as mobile phase B at a flow rate of 0.4 mL/min.Ionization mode ESI+and positive ion multiple reaction monitoring(MRM) mode was adopted for mass spectrometry to collect data.The results showed that 1,4-dimethyl butylene disulfonate,1,4-diethyl butylene disulfonate and 1,4-diisopropyl butylene disulfonate had good linearity in the range of 0.999 6-19.992 0 ng/mL,0.997 2-19.944 0 ng/mL and 0.996 8-19.936 0 ng/mL,with the correlation coefficients of 1.000 0.The limits of quantitation were 0.999 6 ng/mL,0.997 2 ng/mL,0.996 8 ng/mL,and the limits of detection were 0.299 9 ng/mL,0.299 2 ng/mL,0.299 0 ng/mL,respectively.The recoveries of samples were 80%-120%.The method is rapid,simple,sensitive and accurate for the determination of dimethyl 1,4-butanedisulfonate,diethyl 1,4-butanedisulfonate and diisopropyl 1,4-butanedisulfonate in adenomethionine butanedisulfonate enteric-coated tablets,and provides a reference for their quality control.

关 键 词：超高效液相色谱-三重四级杆质谱(UPLC-MS/MS) 丁二磺酸腺苷蛋氨酸 1 4-丁二磺酸酯类 基因毒性杂质 

分 类 号：S859.1[农业科学—临床兽医学]