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.
潘芳芳, 何佳佳, 罗英, 陈悦. 注射用磺苄西林钠的杂质谱研究[J]. 中国药学杂志, 2020, 55(22): 1883-1889.
PAN Fang-fang, HE Jia-jia, LUO Ying, CHEN Yue. Analysis of Impurity Profile of Sulbenicillin Sodium for Injection. Chinese Pharmaceutical Journal, 2020, 55(22): 1883-1889.
YANG Y M, PENG W, ZHANG C Y. Sulbenicillin sodium for injection[J]. China J Mod Med(中国现代医学杂志), 2011, 21(25):3153-3155.
[2]
MA L P, LIU B, LIN Z Q, et al. One case of exfoliative dermatitis induced by sulbenicillin for injection[J]. Chin J Drug Appl Monit(中国药物应用与监测), 2016, 13(6):381-383.
WANG L X, WANG C, ZHANG D S, et al. Quality assessment of domestic sulbenicilin sodium for injection [J]. Chin J Antibiot(中国抗生素杂志), 2017, 42(6):454-459.
[5]
MA X N, FENG F. Determination of unknown impurities in sulbenicillin sodium by liquid chromatogram-mass spectrometry [J]. Cent South Pharm(中南药学), 2011, 9(4):258-261.
[6]
CHANG Y X. Improving Synthetic Process of Sulbencillin Sodium [D]. Tianjing:Tianjing University, 2007.
[7]
XIANG H L, TANG Z Y, YANG X H.Improvement on the synthesis process of sulbenicillin disodium [J]. J China Pharm Univ (中国药科大学学报), 2007, 38(6):496-498.
[8]
HU C Q, JIANG Y, ZHANG J B, et al. Reflection on strategy and methods on trance unstable impurities of β-lactam antibiotic[J]. Chin J New Drugs(中国新药杂志), 2013, 22(1):4-12.
[9]
QIANG J Q.Study on theβ-lactam antibiotics and their impurities fragmentation pathway in mass spectrometry and its toxicity prediction and evaluation [D]. Beijing:Peking Union Medical College Chinese Academy of Medical Sciences, 2014.
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