Determination of Nine Nitrosamine Impurities in Nitroglycerine Injection by HPLC-MS/MS
Objective:To establish an HPLC-MS/MS method for the determination of Nitrosamine impurities in nitroglycerin injection.Method:The method were performed on ACE Excel 3 C18-PFP column(3.0 mm×100 mm,3 μm)with a gradient elution of 0.1％formic acid as the mobile phase A and methanol as the mobile phase B at a flow rate of 0.5 mL·min-1;the column temperature was set at 40℃;the sample plate temperature was 5℃;the injection volume was 5 μL.The ionisation mode was atmospheric pressure chemical ionization positive mode(APCI+)and the detection mode was triple quadrupole mass spectrometry-multiple reaction monitoring(QTOF-MRM);nitrogen was used as drying gas and temperature was 300℃with 4 L·min-1 flow rate;the nebuliser pressure was 40 psi;the capillary voltage was 1500 V;the heater temperature was 350℃and the corona current was 6 μA.Results:Under the detection parameters,each nitrosamine impurity had a good linearity which were between 0.40 ng·mL-1 and 6.65 ng·mL-1,the limits of detection(LOD)was 0.12 ng·mL-1,and the limits of quantification(LOQ)was 0.40 ng·mL-1.The average recovery ranges from 89.7％to 99.3％,and the average RSDs(n=9)were between 3.0％to 5.5％.Three batches of samples were tested and no nitrosamine impurities were detected.Conclusion:This method is simple to operate,highly sensitive and specific,and can be used for the quality control of nine nitrosamine impurities in nitroglycerin injection.
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