Prediction and selection of raw materials for reference standards of cefoxitin sodium

LI Yue-yue; YAO Shang-chen; ZHANG Xia; LIU Wan-hui; HU Chang-qin

Abstract：Objective:To develop a rapid method to predict the long stability of bulk cefoxitin sodium and assist the selection of the raw materials for the reference standard of cefoxitin sodium.Methods:The humiditycorrected Arrhenius equation was used to build the stability prediction model of cefoxitin sodium.The impurity as stability indicator was defined by analyzing the impurity profile of cefoxitin sodium.A high performance liquid chromatographic method was used to quantify the content of the indicative impurity under five different accelerated degradation conditions.The rate constants of degradation reaction were determined based on the principles of zero-order kinetics.Software SPSS 20.0 was applied to build the stability prediction models of cefoxitin sodium from four different manufacturing companies.Results:The equations for the four prediction models were as follows:lnk=26.013/RT +0.004 2 × (RH) + 29.093 for manufacturer A,lnk =25.940/RT + 0.018 6 × (RH) + 29.074 manufacturer B,lnk=15.225/RT + 0.002 6 × (RH) + 13.992 for manufacturer C,and lnk =25.661/RT + 0.011 7 × (RH) + 28.915 for manufacturer D,all R2 of the four prediction models were no less than 0.95 and all P ＜ 0.05,indicating that all the prediction equations had good prediction performance.When the equations were applied to predict the long stability of cefoxitin sodium from four different companies,it was shown that the four products had different stabilities under the same storage condition.Conclusion:The prediction models can be applied not only in the prediction of the long stability of cefoxitin sodium,but also in the determination of storage conditions,transportation conditions and quality supervision circle,providing basis for the selection of raw materials for the reference standard.It was suggested that raw materials with longer stability period be selected based on the prediction model of the raw materials to improve the stability of the reference standard.