超高效液相色谱-串联质谱法测定磷酸肌酸钠中3种潜在遗传毒性杂质  

Determination of three potentially genotoxic impurity in creatine phosphate sodium by ultra-high performance liquid chromatography-mass spectrometry

作　　者：朱永琴[1] 张俊朋 连莹[1] 陈杰[1] 朱赞梅 毛影 ZHU Yongqin;ZHANG Junpeng;LIAN Ying;CHEN Jie;ZHU Zanmei;MAO Ying(Henan Provincial Institute for Food and Drug Control,Zhengzhou 450018,Henan Province,China;Kaifeng Mingren Pharmaceutical co.LTD,Kaifeng 450000,Henan Province,China)

机构地区：[1]河南省食品药品检验所,河南郑州450018 [2]开封明仁药业有限公司,河南开封450000

出　　处：《新乡医学院学报》2020年第4期323-326,共4页Journal of Xinxiang Medical University

基　　金：科技部“重大新药创制”科技重大专项(编号:2017ZX09101001)。

摘　　要：目的建立同时测定磷酸肌酸钠中3种潜在遗传毒性杂质磷酸三乙酯、肌酸磷酸二乙酯、肌酐磷酸二乙酯含量的超高效液相色谱-质谱法(UPLC-MS)。方法采用超高效液相色谱-三重四极杆质谱联用仪,色谱柱ACQUITY UPLC BEH C18(2.1 mm×10 cm;1.7μm);流动相为0.1%甲酸水溶液-甲醇(60∶40);流速为0.25 mL·min^-1;柱温为30℃;进样量为20μL;电喷雾离子源,正离子模式,多反应监测扫描方式采集数据。结果磷酸三乙酯、肌酸磷酸二乙酯、肌酐磷酸二乙酯分别在0.5~135.6、4.1~103.9、0.8~125.6μg·L^-1,峰面积与浓度呈良好线性关系;检测限分别为0.2、1.3、0.3μg·kg^-1;定量限分别为0.6、4.1、0.9μg·kg^-1;在高、中、低3个加标水平下,3种杂质的回收率为97.4%~103.8%,相对标准偏差为0.3%~2.8%。结论该方法简便准确,可用于磷酸肌酸钠中磷酸三乙酯、肌酸磷酸二乙酯、肌酐磷酸二乙酯等杂质的检测。Objective To establish a ultra-high performance liquid chromatography-mass spectrometry analytical method for determination of triethyl phosphate,diethyl creatine phosphate and creatinine diethyl phosphate which are potentially genotoxic impurity in creatine phosphate sodium.Methods Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used.The best separation was achieved by an ACQUITY UPLC BEH C18(2.1 mm×10 cm;1.7μm),utilized a mobile phase of water(containing 0.1%formic acid)-methanol(60∶40)at the flow rate of 0.25 mL·min^-1.The temperature of column was set at 30℃,the injection volume was 20μL.Molecular ions were generated by using the positive electrospray ionization mode with multiple reaction monitoring and they were analyzed on a triple-quadrupole mass spectrometer.Results Good linear correlations of triethyl phosphate、diethyl creatine phosphate and creatinine diethyl phosphate were observed in the range of 0.5-135.6,4.1-103.9,0.8-125.6μg·L^-1;the limit of detection was 0.2,1.3,0.3μg·kg^-1 respectively;the limit of quantification was 0.6,4.1,0.9μg·kg^-1,respectively.The average recoveries at low,medium,and high spiked levels ranged from 97.4%to 103.8%with relative standard deviations of 0.3%-2.8%.Conclusion The method is convenient and sensitive for the determination of triethyl phosphate,diethyl creatine phosphate and creatinine diethyl phosphate in creatine phosphate sodium.

关 键 词：磷酸肌酸钠 潜在遗传毒性杂质 超高效液相色谱-质谱法 

分 类 号：R917[医药卫生—药物分析学]