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.
作者
朱永琴
张俊朋
连莹
陈杰
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)
出处
《新乡医学院学报》
CAS
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)。
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
creatine phosphate sodium
potential genotoxic impurities
ultra-high performance liquid chromatographymass spectrometry
