2D-HPGFC-RPLC-MS Method for Characterization of Polymer Impurities in Azlocillin Sodium for Injection / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish a method for the separation and characterization of polymer impurities in azlocillin sodium for injection, and evaluate the efficacy of high performance gel filtration chromatography(HPGFC) method for determination of the polymer impurities. METHODS: Using two-dimensional HPGFC and reversed-phase liquid chromatography(RPLC)-mass spectrometer, an Ultimate SEC-120 column was used in the first dimensional chromatography, with isocratic elution using 5 mmol·L-1 phosphate buffer (pH 7.0) as the mobile phase. An XBridge C18 column was used in the second dimensional chromatography, with gradient elution using 10 mmol·L-1ammonium formate solution(pH 6.5) and 8 mmol·L-1ammonium formate in mixture of acetonitrile and water (200∶50) as the mobile phase. Two mass spectrometers with ESI source were used for 2D-LC-MSn. RESULTS: The polymer impurities found by HPGFC also included penicillenic acid of azlocillin and decarboxylated penicillenic acid of azlocillin. The chemical structures of four polymer impurities identified in the second dimensional RPLC were elucidated. CONCLUSION: The 2D-HPGFC-RPLC-MS method can be used to profile the polymer impurities in azlocillin sodium for injection, which is helpful to realize effective control over polymer impurities in β-lactam antibiotics.