关键词: font-size:medium, ">超高效液相色谱-四级杆/静电场轨道阱高分辨质谱法（UHPLC-Q-Orbitrap HRMS）；遗传毒性杂质；盐酸二甲双胍；杂质C

Abstract: Objective： To establish a rapid ultra high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry（UHPLC-Q-Orbitrap HRMS）method for determination of genotoxic impurity in metformin hydrochloride and its tablets. Methods： The analyte was separated on Waters ACQUITY UPLC BEH Shield RP18（2.1 mm×100 mm，1.7 μm）column with 10 mmol·L-1 ammonium formate solution-acetonitrile（90∶10）as the mobile phase. The flow rate was set at 0.2 mL·min-1.The target compound was analyzed by the positive ion parallel reaction monitoring（PRM）mode. Results： The methodological evaluation showed that this method had good specificity， repeatability and stability. The linear range of impurity C was 0.625 6-3.910 2 ng·mL-1（r=0.999 7）， the recovery of drug substance and tablets were 87.6% and 86.4%. The content range of impurity C in samples was 3.5-11.0 μg·g-1. Conclusion： This method is simple， accurate and reliable， and is suitable for the rapid detection of impurity C in metformin hydrochloride and its tablets. And this method will lay a reference for the similar impurities in other drugs.
   

Key words: font-size:medium, ">UHPLC-Q-Orbitrap HRMS； Genotoxic impurity； Metformin hydrochloride； Impurity C