Research On The Impurities Of Adenosine Cyclophosphate For Injection

The standard of Adenosine Cyclophosphate for Injection is collected in the Chinese Pharmacopoeia 2010.But in the quality evaluation of post-marketing,it was found that the method for organic impurities’ test in this standard need to be improved.In this thesis two main researches had been done:one is the improvement of current detection method of organic impurity,the other is the structural identification and cluster analysis of organic impurities due to adenosine cyclophosphate.The results are as follow:1.The research on the retention time of impurities:Not all peaks of impurities can be recorded within 2.5 times of the main peak’s retention time,so the record time of the chromatogram should be prolonged to 10 times the retention time of main peak.And one kind of C18 column is recommended.To avoid the misdetection of impurities,the concentration of test solution had been raised to 1mg/ml.2.The research on the system suitability test:The main decomposition products of adenosine cyclophosphate under acid degradation are 2’-AMP and 3’-AMP.The main decomposition product under alkaline degradation is 3’-AMP.According to the research result,it was advised that adenosine cyclophosphate,2’-AMP and 3’-AMP should be included in system suitability test solution.3.The results of impurity test on 91 batches of sample with optimized method:The numbers and the quantity of impurities were higher than those obtained with original method.It’s the real reflection of sample quality.According to research,the method should be improved,and the limit of single impurity should be controlled.4.The identification of the unknown impurities by HPLC-MS:Three impurities were identified,which are dimer of adenosine cyclophosphate(peak 12),isomer of adenosine cyclophosphate(peak 14)and N-dimethyl adenosine cyclophosphate(peak 17).5.Impurity profile study of adenosine cyclophosphate preparations:The analysis shows the impurities of Adenosine Cyclophosphate for Injection can be separated into two categories,which are in accordance with its API manufacturers.