Analysis of Impurity Profile of Cefotaxime Sodium by HPLC-MS
HOU Yu-rong1, HUANG Min-wen1,2, ZHAO Li-li3, SU Nan3, JI Wen-dan4, YUAN Yao-zuo1*, ZHANG Mei1, HANG Tai-jun3
1. Jiangsu Institute for Food and Drug Control, Nanjing 210008, China; 2. Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China; 3. Jiangsu Institute for Drug Control, Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China; 4. Jiangsu Yukang Pharmaceutical Co., Ltd., Wuxi 214000, China
Abstract��OBJECTIVE To establish an HPLC-MS method for the analysis of the impurity profile of cefotaxime sodium. METHODS Shimadzu-LCMS-IT-TOF was used with Waters XBridge Shield (RP18,4.6 mm��250 mm, 5 ��m) column. Mobile phase A was 20 mmol��L-1 ammonium acetate (pH adjusted to 6.25)-methanol (92:8), and mobile phase B was set at 20 mmol��L-1 ammonium acetate-methanol (60:40) (pH adjusted to 6.25).Gradient elution was performed at a flow rate of 1.0 mL��min-1. ESI source was used.Positive and negative ion scanning was conducted in the range of m/z 150-900.The heating temperature was 200 ��, CDL temperature was maintained at 200 ��, atomization gas flow rate was 1.5 L��min-1, dry gas pressure was 94.0 kPa, and the post-column diversion ratio was 1:4.Some related substances in cefotaxime sodium were identified by comparing the retention time in chromatography,[M+H]+ spectrum and MS2 spectrum with those of reference substances, the others which haven't reference substances were deduced or speculated by analyzing the MS2 or MSn fragmentation with the help of a rule summarized from the MS2 fragmentation of cefotaxime sodium and the reference substances of system suitability impurities. RESULTS Twenty-six related substances were separated and detected in the sample, all of which were identified or deduced. They were cefotaxime sodium isomeric compounds and homologs generated during the production process or degradation products. CONCLUSION The method can be applied in the identification and qualitative analysis of the related substances of cefotaxime sodium and the quality control and optimization of the synthesis of cefotaxime sodium.
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2017, Vol. 52 
