Determination of trace N-nitrosodimethylamine in Ranitidine and its preparation by liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry
WEI Zhixiong1 LIU Dandan1 LAN Mingxiong1 WANG Kunpeng1 LI Ru2
1.Dongguan Institute for Food and Drug Control,Guangdong
2.College of pharmacy,Guangdong Medical University
Abstract：Objective To determine the content of N-nitrosodimethylamine (NDMA) in ranitidine and its preparations by liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry (HPLC-Orbitrap HRMS).Methods The separation was performed on an ACE EXCEL 3 C18-AR(4.6 mm×100 mm,3 μm)column with mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in acetonitrile by gradient elution.The flow rate was 0.50 ml/min.The column temperature was 30℃,and the temperature of the injector was 4℃.The MS analysis was performed with ESI ion source in positive ion parallel reaction monitoring (PRM) scanning mode,and external standard method were used for quantification.Results NDMA with a good linear relationship in the range of 1-75 ng/ml (r=0.9990).The RSD of precision determination at the concentrations of 2 ng/ml and 20 ng/ml were 0.5% and 1.3% respectively,which were far less than 10%.The recoveries were 97.4%-105.2% with RSD of 2.5% (n=6).The limit of detection and limit of quantification were 0.03 ng/ml and 0.10 ng/ml,respectively.The established method was used to determine 7 batches of ranitidine active pharmaceutical ingredient (API) and ranitidine capsules.The results showed that the content of NDMA was among 0.12-2.36 ppm.Conclusion This method is specific,sensitive,accurate and simple,and can be applied to the determination of trace NDMA in ranitidine API and its preparations.
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WEI Zhixiong；LIU Dandan；LAN Mingxiong； WANG Kunpeng；LI Ru. Determination of trace N-nitrosodimethylamine in Ranitidine and its preparation by liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry. 中国当代医药, 2022, 29(7): 15-19.
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