Revision Of Quality Standards For Cefquinome Sulfate And Its Preparations

Cefquinome Sulfate,as the fourth-generation animal-specific cephalosporin antibiotic,was successfully developed by Hoechst Roussel Vet Company in Germany in the 1980s.Since 2008,a variety of veterinary drug manufacturers in China have independently developed cefquinome sulfate,cefquinome sulfate for injection and cefquinome sulfate injection,and registered as national second-class new veterinary drugs.The Ministry of Agriculture also issued the corresponding quality standards for veterinary drugs.A variety of veterinary drugs with multiple standards can be seen thereafter.To regulate and improve the quality standards for veterinary drugs,the "Chinese Veterinary Pharmacopoeia"(2015 Edition)is intended to record standards for cefquinome sulfate,cefquinome sulfate for injection,and cefquinome sulfate injection based on the characteristics of veterinary use.Jiangsu Testing Institute of Veterinary Drug and Feed that the author is working in has undertook the task of revisions,investigating the original seven quality standards of cefquinome sulfate,cefquinome sulfate injection and cefquinome sulfate for injection,and carrying out a verification and partial revision in terms of their definitions and limits,sample traits,identification methods,and inspection items related to safety and stability,as well as content determination.The revision contents of quality standards for raw materials of cefquinome sulfate:1.A thermodynamic analysis against the cefquinome sulfate was carried out to confirm that it does not contain crystallization water,so its chemical name was revised accordingly;2.The dissolution status of the samples in different solvents was tested,and the solubility descriptions of sample traits were revised;3.The impurity localization of 5,6,7,8-tetrahydroquinoline was added to related substance inspection items,and the area normalization method and self-reference method got compared and the results seemed consistent;4.The content determination(PHLC)method was verified to prove that it is very specific,the blank and impurities do not interfere with the samples,and the components that may exist in the samples can be completely separated;the precision is favorable,the RSD remains 0.1%;the linearity is found good when the sample solubility is in the range of 10?g/ml-500?g/ml,and the correlation coefficient R2=0.99999.Changing the flow ratio within a certain range,column temperature,and selecting different brands of chromatographic columns will not affect the experimental results and good durability can be ensured.The revision contents of quality standards for cefquinome sulfate for injection:1.In the original standards,the coloration identification was carried out based on the physicochemical properties of ?-lactam ring in cefquinome sulfate,and its specificity was proven not strong,so deletion is recommended;2.The impurity localization of 5,6,7,8-tetrahydroquinoline was added to related substance inspection items,and the area normalization method and self-reference method got compared and the results seemed consistent;3.The sterility test was adopted to confirm the dilution method and rinse volume of the samples.The positive bacteria grow well after validation.4.The content test items were adopted to verify the accuracy of the method.The recoveries were 80%,100%,and 120%,and the average recoveries were 98.8%,99.7%,and 100.2%,which were in accordance with the requirements.The revision contents of quality standards for cefquinome sulfate injection:1.Through a comparison of tests,the extraction method of the samples for[Related substances]and[Assay]was determined,and the original "water bath ultrasound" was revised to "strong vibration for 10 minutes";2.Via a verification test,the amount of samples taken in the sterility test,the dilution factor and the amount of penicillinase usage were determined;and the membrane filtration method was compared with the direct inoculation method,which was proven more applicable;3.The particle size range of the samples was determined.Results have shown that the particle size can be controlled "not less than 90%when the particles is below 15 ?m";4.The assay items were adopted to verify the accuracy of the method.The recoveries were 80%,100%,and 120%,and the average recoveries were between 99%and 103%,which were in accordance with the requirements.