摘要
目的:采用高效液相色谱-四极杆飞行时间质谱(LC-Q-TOF-MS)建立氯沙坦钾及其复方制剂中基因毒性杂质N-亚硝基-N-甲基-4-氨基丁酸(NMBA)的测定方法。方法:采用Agilent ZORBAX SB-C18色谱柱(2.1 mm×50 mm,1.8μm)进行分离,流动相为0.1%甲酸水溶液-乙腈,梯度洗脱,流速0.3 mL·min^-1;质谱采用电喷雾离子源,正离子模式下选择[M+H]+m/z 147.076 4对NMBA进行测定。结果:NMBA在5~100 ng·mL^-1浓度范围内线性良好,相关系数为0.995 6。定量下限(LOQ)为2.1 ng·mL^-1,精密度试验和重复性试验RSD均小于10.0%。3批药品中均未检出NMBA。结论:本方法可用于氯沙坦钾及其复方制剂中NMBA的测定。
Objective:To determine the genotoxic impurity N-nitroso-N-methyl-4-amimobutyric acid(NMBA) in losartan potassium and its compound preparation by high performance liquid chromatography-quadrupole-timeof-flight mass spectrometry(LC-Q-TOF-MS). Methods:The separation was carried out on an Agilent ZORBAX SB-C18 column with the mobile phase consisting of 0.1% formic acid-water solution and acetonitrile. The flow rate was 0.3 mL·min^-1 with gradient elution. Electronic spray ion(ESI)in positive ionization mode was performed and [M+H]+ m/z 147.0764 was extracted for the determination. Results:The calibration curve of NMBA was in good linearity with a correlation coefficient of 0.995 6 in the range of 5~100 ng·mL^-1. The limit of quantification(LOQ) of NMBA was 2.1 ng·mL^-1,and RSDs of both precision and repeatability tests were less than 10.0%. NMBA was not detected in the three batches of samples. Conclusion:The method can be used to determine NMBA in potassium losartan and its compound preparations.
作者
徐文峰
金鹏飞
徐硕
张闪闪
吴学军
XU Wen-feng;JIN Peng-fei;XU Shuo;ZHANG Shan-shan;WU Xue-jun(Department of Pharmacy,Beijing Hospital,National Center of Gerontology,Assessment of Clinical Drugs Risk and Individual Application Key Laboratory,Bejing 100730,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2019年第11期2047-2050,共4页
Chinese Journal of Pharmaceutical Analysis
基金
北京医院科技新星项目(BJ-2016-039)
国家自然科学基金项目(81803715)
