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

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，1.8 μm）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-time-of-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.

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