Determination of four genotoxic impurities in flurbiprofen by high performance liquid chromatography
Objective To establish a HPLC method for the determination of genotoxic impurities in flurbiprofen:2-fluoroaniline,4-bromo-2-fluoroacetanilide,4-bromo-2-fluoroaniline and 4-bromo-2-fluorobenzene.Methods The separation was performed on a Phenomenex Kinetex F5 100A column(250 mm ×4.6 mm,5 μm)using the mobile phase consisting of acetonitrile-water-glacial acetic acid(V∶V∶V=30∶65∶5)(mobile phase A)and acetonitrile(mobile phase B)by gradient elution at a flow rate of 1.2 mL·min-1.The detection wavelength was 254 nm,the injection volume was 10 μL and the column temperature was 35 ℃.Results The detection limits of 2-fluoroaniline,4-bromo-2-fluoroacetanilide,4-bromo-2-fluoroaniline and 4-bromo-2-fluorobenzene were 5.987,3.198,6.408,3.199 μg·mL-1,Standard curves of them were linear within the range of 19.96-2 235(r=0.993),10.66-2 387(r=0.999),21.36-2 392(r=0.999)and 10.66-2 388 mg·L-1(r=0.999).The average recoveries were 100.5％,100.2％,101.4％and 97.9％(n=9).The control solution and the labeled sample solution were stable within 24 h.The genotoxic impurities in the three batches of samples were all in the limit requirements.Conclusion The established method is simple,accurate and specific,suitable for the determination of 2-fluoroaniline,4-bromo-2-fluoroacetanilide,4-bromo-2-fluoroaniline and 4-bromo-2-fluorobenzene in flurbiprofen.
high performance liquid chromatographyflurbiprofengenotoxic impurity
万方数据
维普
