LC-Q-TOF-MS法测定氯沙坦钾及其复方制剂中痕量杂质N-亚硝基-N-甲基-4-氨基丁酸  

Determination of trace impurity NMBA in potassium losartan and its compound preparations by LC-Q-TOF-MS

作　　者：徐文峰[1] 金鹏飞[1] 徐硕[1] 张闪闪 吴学军[1] 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)

机构地区：[1]北京医院药学部国家老年医学中心药物临床风险与个体化应用评价北京市重点实验室

出　　处：《药物分析杂志》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)

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.

关 键 词：氯沙坦钾 复方制剂 N-亚硝基-N-甲基-4-氨基丁酸 基因毒性杂质 高效液相色谱-四极杆飞行时间质谱 含量测定 

分 类 号：R917[医药卫生—药物分析学]