Abstract: OBJECTIVE To establish an HPLC-MS/MS method for the determination of amines,open-chain amides and hydrazine based compound in apixaban.METHODS Separation was performed on a Zobax Eclipse XDB C₁₈(3.0 mm×150 mm,3.5μm).Amines and open-chain amides were separated with the mobile phase of 10 mmol·L^-1 ammonium acetate solution and acetonitrile in gradient elution.Hydrazine based compound was separated with the mobile phase of water-methanol(30:70) in isocratic elution.The electrospray ionization source with positive ion mode was used for structure confirmation in the multiple reaction monitoring(MRM) mode.RESULTS The average recoveries for the determination of amines,open-chain amides and hydrazine based compounds were 99.6%,92.2%and 97.5%,RSDs were 3.8%,1.9%and 7.2%(n=9),respectively.Limits of quantitation were 0.05,0.05 and 0.05 ng·mL^-1.CONCLUSION The method can effectively eliminate the matrix effect and can be used for the quantitative determination of amines,open-chain amides and hydrazine based compound in apixaban.