The Compatibility Of Cephalosporin And Rubber Stoppers

Cephalosporin antibiotics are a kind of antibiotics commonly used in clinic.The quality of safe,effective and controllable related to people's life and health.The most prominent quality problem is the disqualification of cephalosporin clarity,clinically apt to cause allergic reactions,which threaten the life safety of patients.Butyl rubber stopper is a kind of drug packaging material,which is commonly used in the injectable cephalosporin.Its production process is complex,and the chemical additives and residues in the process will remain in the body of the rubber stopper,which lead to many uncontrollable factors in the quality of butyl rubber stopper.The butyl rubber stopper is contacted directly with the drug powder during the storage of injectable cephalosporin.Some of the volatiles of rubber will interact with cephalosporin and adsorption is the most important reason for the disqualification of cephalosporin.The cephalosporin with poor compatibility between the drug and butyl rubber stopper is more likely to produce the problem of disqualification.Nowadays,the compatibility test between rubber stopper and cephalosporin is of great importance to evaluate cephalosporin quality and it has attracted extensive attention.However,the following problems still exist in the compatibility test: There are many kinds of volatile compounds and complex components in rubber stopper.The volatile components in different kinds of medicinal rubber stopper are uncertain.Different cephalosporin has different compatibility with different rubber stopper,so it is difficult to select suitable rubber stopper.Based on the above problems,this paper has carried on the following research:Firstly,HS-GC-MS(headspace gas chromatography-mass spectrometry)was used to analyze volatiles in rubber stoppers from different factories.The species and structure of the part of volatiles in rubber stoppers were fully understood.Then the structure of volatiles in some rubber stoppers was confirmed.The cluster analysis of the rubber stopper was carried out according to the normalized content of the peak area of the main volatiles.Then the quality evaluation of different kinds of rubber stopper was carried out according to the result of cluster analysis.Secondly,a database for matching the GC retention time information and GC-MS retention time information of double column system was established,for establishing a rapid screening system for volatiles in rubber stoppers.A database for matching volatiles inclusion of polar column and nonpolar column under GC-MS condition was established,which contributes to the overall screening of volatiles in rubber stoppers.Thirdly,the difference of volatile components between cefazolin sodium and cefazolin sodium pentahydrate after adsorbtion with rubber stoppers and the results show that cefazolin sodium pentahydrate adsorb less volatiles.We can draw a conclusion that the compatibility of cefazolin sodium pentahydrate and the rubber stopper is better than cefazolin sodium.Finally,the correlation between the turbidity of the model drugs,cefazolin sodium,ceftriaxone sodium,cefotaxime sodium and montelukast sodium and the type and content of the adsorbed rubber stopper volatiles were investigated,and validated by cross experiment and simulated adsorption test.The adsorption relationship of the structure of the cephalosporins and volatile compounds of rubber stoppers is discussed.In this paper,the rubber stoppers and cephalosporins were used as subjects and HS-GC-MS was used as the main method of analysis.On the one hand,the types and content of volatiles in rubber stopper were analyzed.On the other hand,the correlation between the turbidity value of different cephalosporins and the types of rubber stopper volatiles was analyzed,to investigate the effect of cephalosporin structure on adsorption.It can guide the pharmaceutical enterprises to select suitable rubber stoppers and evaluate the quality of cephalosporins.