Abstract：OBJECTIVE To establish an HPLC-MS method for analysis of the impurity profile of sulbenicillin sodium for injection and confirm their coming source. METHODS Agilent 1290 HPLC-6538 Q-TOF was used,and the column was Ultimate XB C18(4.6 mm×250 mm,5 μm). The mobile phase was 10 mmol·L-1 ammonium formate and 8 mmol·L-1 ammonium formate (solvent was 80% acetonitrile solution)(87∶13). The flow rate was 1.0 mL·min-1. ESI source was used. Negative ion scan was conducted with a scanning range of m/z 50-1 000. Post-column diversion ratio was 1∶2. Then capillary voltage was 3.5 kV and taper hole voltage was 65 V. The nebulizing pressure was 310 kPa and dry gas(N2) flow was 12 L·min-1. The dry gas temperature was 325 ℃. The cataclastic voltage was 150 V. Then the unknown impurities were deduced by comparing the similarities and difference with sulbenicillin in mass spectrum as well as the production process. RESULTS Fourteen related substance were separated and detected in the samples from five manufacturers. Their structures were identified by analyzing their fragmentation pathway in MS. And the sources were determined. CONCLUSION The method is helpful for the quality control of sulbenicillin sodium for injection and optimization of the synthetic process.
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