Study On Quality Control Of Morphine Sulfate Preparation

Objective:According to pharmacopoeia at home and abroad and drug quality standards of various countries,a complete and feasible quality standard of morphine sulfate tablet and morphine sulfate injection is established,so as to strictly control the quality of morphine sulfate preparation and ensure the safety and rationality of clinical drug use.Methods:1.Study on quality control of morphine sulfate tablets:（1）To establish HPLC method for determination of relevant substances in morphine sulfate tablets,and according to a series of methodological experiments such as stability and specificity,analyze the source of each impurity and formulate the relevant impurity limits;（2）To establish HPLC method for content determination and content uniformity of morphine sulfate tablets,and determine chromatographic conditions and pre-treatment conditions through methodological verification;（3）To establish the dissolution method of morphine sulfate tablets with paddle method and HPLC determination method,and determine the extraction parameters such as dissolution medium,sampling time and related chromatographic conditions.2.Study on quality control of morphine sulfate injection:（1）To establish HPLC method for determination of substances related to morphine sulfate injection through methodological verification and define limits of impurities;（2）According to the accumulate calculation results of enterprise feeding for many years and the concentration provisions of sodium pyrosulfite in Chinese Pharmacopoeia,establish a reasonable upper limit of sodium pyrosulfite inspection items;（3）To establish HPLC method for content determination of morphine sulfate injection and revise content limit.Results:1.Study on quality control of morphine sulfate tablets:（1）Related substances:methodological results are good,the limits of impurities are:Impurity A（codeine）is 0.2%,impurity B（pseudo-morphine）is 0.5%,impurity C（Oleba）is 0.2%,impurity D（10-hydroxymorphine）is 0.2%,impurity E（morphone）is 0.5%,impurity F（morphine nitrogen oxide）is 0.2%,other single impurities are 0.5%,total impurities are 2.0%.One batch of samples is not up to standard;（2）Content uniformity and content determination items:the methodological results are good,and the content uniformity and content determination results of three batches of morphine sulfate tablets all meet the requirements;（3）Dissolution test items:determine water as dissolution medium,sampling time using30min paddle method,determination method is the same as content determination method downward,three batches of morphine sulfate tablets dissolution test results are qualified;2.Study on quality control of morphine sulfate injection:（1）Related substance inspection items:the detection method was consistent with the original Chinese standard,and the methodological results are good,and three batches of samples are qualified;（2）Sodium pyrosulfite examination items:the content of sodium pyrosulfite in the test product should be0.5 mg·m L^-1～1.1 mg·m L^-1,and the sample determination results are 0.8 mg·m L^-1,0.8mg·m L^-1,0.7 mg·m L^-1;（3）Content determination items:HPLC detection method in the original standard are adopted,and all three batches of samples are qualified.Conclusion:1.Study on quality control of morphine sulfate tablets:update related substance inspection items and related impurity limits;The original UV method are improved to HPLC method.;The dissolving method of the original standard small cup method in China is improved to paddle method.Formed a complete quality standard of morphine sulfate tablets.2.Study on quality control of morphine sulfate injection:revise the limit of remaining impurities and the upper limit of sodium pyrosulfite in related substance inspection items;Increase the original content limit;A complete draft quality standard was formed,and the original standard was further improved.