Identification And Quality Control Of Major Degradation Impurities In Pantoprazole Sodium For Injection

This paper did literature retrieval and special investigation about pantoprazole sodium for injection.Considering the medcine’s starting materials,producng processes,quality standards and instructions,this paper studied deeply on four points:the related substance,the effect of compatibility solution on stability of pantoprazole sodium,analysis of degradation impurities and the adding amount of EDTA-Na₂,which could influence the safety of patients who took this medcine.The method of relevant substance of pantoprazole sodium for injection in USP37 is similar to the method in EP8.0.Also,their limits of impurities are slightly different.But there is obvious difference between the method in ChP2015 and the two methods mentioned above.So this paper compared the method in ChP2015 with the method in USP37.The results showed that the method in ChP2015 could completely separate known impurities of USP and detected them effectively.The retention time in ChP2015 was close to the retention time in USP37.The results of impurities content were also the same.Pantoprazole sodium is alkaline drug,which is stable in alkaline solution.The instructions said that it should be dissolved with 0.9% NaCl injection and be injected in a certain time.So the pH of NaCl injection had great importance on the security of pantoprazole sodium.This paper did research on it.The results showed that the content of pantoprazole sodium decreased and impurities increased with aging time.With the pH of NaCl injection decreasing,the degradation rates increased gradually.According to the above research,the selection of compatible solution is suggested.As stated above,the solution of pantoprazole sodium degraded with aging time.And the existence of impurities might influence the quality of pantoprazole sodium,which might lead to serious adverse reactions and influence people’s health.As a result,analysis of degradation impurities was very important.So this paper refined the method based on the method in ChP2015.Finally,it established suitable chromatographic conditons of LC-MS and seperated degration impurities effectivelywith gradient elution.It analysed the degradation impurities’ structures with HPLC-Q-TOF and tried to confirm the results with HPLC-NMR.The source of main degration impurities was also analysed.To improve the stability of injections,some manufactories added EDTA-Na₂ to pantoprazole sodium for injection.But EDTA-Na₂ could also combined with calcium ions within body and then be evacuated.Excessive take of EDTA-Na₂ might lead to hypocalcemia or calcium loss.So it’s necessary to carry out exploratory research on the aiding condition of EDTA-Na₂.This paper established HPLC-method and complex method to determine the content of EDTA-Na₂ and evaluated the results.