[1]朱永琴,张俊朋,连　莹,等.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[J].新乡医学院学报,2020,37(4):323-326.[doi:10.7683/xxyxyxb.2020.04.005]
　ZHU Yongqin,ZHANG Junpeng,LIAN Ying,et al.Determination of three potentially genotoxic impurity in creatine phosphate sodium by ultra-high performance liquid chromatography-mass spectrometry[J].Journal of Xinxiang Medical University,2020,37(4):323-326.[doi:10.7683/xxyxyxb.2020.04.005]
点击复制

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
分享到：

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
37
期数:
2020年4
页码:
323-326
栏目:
基础研究
出版日期:
2020-04-05

文章信息/Info

Title:
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1; 连　莹1; 陈　杰1; 朱赞梅2; 毛　影2
（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）
Author(s):
ZHU Yongqin1; ZHANG Junpeng1; LIAN Ying1; CHEN Jie1; ZHU Zanmei2; MAO Ying2
(1.Henan Provincial Institute for Food and Drug Control，Zhengzhou 450018，Henan Province,China；2.Kaifeng Mingren Pharmaceutical co.LTD，Kaifeng 450000，Henan Province,China)
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
Keywords:
creatine phosphate sodium; potential genotoxic impurities; ultra-high performance liquid chromatography-mass spectrometry
分类号:
R917
DOI:
10.7683/xxyxyxb.2020.04.005
文献标志码:
A
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；1.7 μm）；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20 μL；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、0.8～125.6 μg·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、0.3 μg·kg-1；定量限分别为0.6、4.1、0.9 μg·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。
Abstract:
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；1.7 μm），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 20 μL.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 0.5-135.6,4.1-103.9,0.8-125.6 μg·L-1；the limit of detection was 0.2,1.3,0.3 μg·kg-1 respectively；the limit of quantification was 0.6,4.1,0.9 μg·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.

参考文献/References:

［1］　王萍，徐彩虹，陈仙，等．原料药中基因毒性杂质控制的研究进展［J］．中国现代应用药学，2015，32(1)：119-126.
［2］　EMEA.Guideline on the limits of genotoxic impurities.committee for medicinal products for human use［S］.Committee for Medicinal Products for Human Use(CHMP),2006.
［3］　EMEA.Questions and answers on the guideline on the limits of genotoxic impurities ［S］.Committee for Medicinal Products for Human Use(CHMP),22010.
［4］　FDA.Guidance for industry genotoxic and carcinogenic impurities in drug substances and products:recommended approaches (Draft Guideline) ［S］.Food and Drug Administration(FDA),2008.
［5］　SINGH J.International conference on harmonization of technical requirements for registration of pharmaceuticals for human use［J］.J Pharmacol Pharmacother.2015,6(3):185-187.
［6］　黄萍．浅析心血管疾病中使用磷酸肌酸钠的临床效果［J］．当代医学，2016，22(12)：128-129.
［7］　曹甦，姚惠辉，牛锋．磷酸肌酸钠治疗儿童病毒性心肌炎疗效观察［J］．新乡医学院学报，2019，36(7)：670-672.
［8］　王萍，徐彩虹，陈仙，等.原料药中基因毒性杂质控制的研究进展［J］．中国现代应用药学，2015，32（1）：119-126.
［9］　李海霞，白培锋，刘娜，等．卡非佐米中基因毒性杂质和吗啉乙酸的LC-MS/MS法测定［J］．中国医药工业杂志，2016，47(10)：1308-1310 .
［10］　阮晓玲，郑项元，徐洁，等．药物中基因毒性杂质分析方法的研究进展［J］．中国药科大学学报，2016，47(3)：267-274.
［11］　刘雪薇，厉程，韩海云，等．药物中磺酸酯类基因毒性杂质研究进展［J］．色谱，2018，36(10)：952-961.
［12］　叶晓霞，吴静雯，乐健，等．富马酸替诺福韦二吡呋酯中基因毒性杂质溴乙烷的GC-MS/MS法测定［J］．中国医药工业杂志，2018，49(12)：1701-1704.
［13］　陈爽，黄巧巧.左氧氟沙星中潜在基因毒性杂质二氯亚砜的GC-MS法测定［J］．海峡药学，2019，31(5)：54-56.
［14］　杨志雄,周小华,赵春花,等.固定化肌酸激酶柱连续合成磷酸肌酸工艺［J］.药物生物技术,2015(3)：213-217.
［15］　陈宁.磷酸肌酸钠的合成［J］.广州化工，2016，44（23）：48-50.
［16］　练美华.磷酸肌酸钠的合成［J］.中国医药工业杂志，2013,44(7) : 655-657.

相似文献/References:

[1]曹　甦,姚惠辉,牛　锋.磷酸肌酸钠治疗儿童病毒性心肌炎疗效观察[J].新乡医学院学报,2019,36(7):670.[doi:10.7683/xxyxyxb.2019.07.017]
　CAO Su,YAO Hui-hui,NIU Feng.Effect of creatine phosphate sodium in treatment of viral myocarditis in infants[J].Journal of Xinxiang Medical University,2019,36(4):670.[doi:10.7683/xxyxyxb.2019.07.017]
[2]刘利利.磷酸肌酸钠对缺氧缺血性脑病并发心肌损伤新生儿心功能及炎症反应的影响[J].新乡医学院学报,2019,36(6):554.[doi:10.7683/xxyxyxb.2019.06.014]
　LIU Li-li.Effect of creatine phosphate sodium on cardiac function and inflammatory response in neonates with hypoxic ischemic encephalopathy combined with myocardial damage[J].Journal of Xinxiang Medical University,2019,36(4):554.[doi:10.7683/xxyxyxb.2019.06.014]
[3]傅洪瑞.磷酸肌酸钠联合喜炎平注射液治疗小儿轮状病毒性肠炎合并心肌损害的临床效果及对患儿心肌酶谱水平的影响[J].新乡医学院学报,2017,34(8):741.[doi:10.7683/xxyxyxb.2017.08.021]
　FU Hong-rui.Clinical effect of creatine phosphate sodium and Xiyanping injection for treat of children with rotavirus enteritis complicated with myocardial injury and it′s influence on myocardial enzymes changes[J].Journal of Xinxiang Medical University,2017,34(4):741.[doi:10.7683/xxyxyxb.2017.08.021]

更新日期/Last Update: 2020-04-05