影响注射用头孢拉定/精氨酸含量测定准确性的因素探讨___

目的：探讨影响注射用头孢拉定/精氨酸含量测定准确性的因素。方法：通过对2批仲裁注射用头孢拉定/精氨酸的分析，按照中国药典2005年版方法测定头孢拉定含量，用HPCE法（内标法）测定精氨酸含量，同时考察杂质头孢氨苄含量、精氨酸含量、装量、样品的稳定性、样品的引湿性、样品溶解超声时间和取样方式对头孢拉定含量测定结果的影响，分析之间的相关性，寻找易造成头孢拉定/精氨酸含量测定结果偏差的主要原因。结果：由于终产品为头孢拉定和精氨酸的混合物，头孢拉定粉末和精氨酸粉未在物理性质上的差异会造成两者在样品瓶中的不均匀分布，从而导致头孢拉定和精氨酸含量测定结果之间存在较大的差异，5瓶样品之间头孢拉定含量测定结果极差可达近8%，RSD为3.0%。结论：复方制剂中头孢拉定和精氨酸的混合均匀性是引起含量测定结果差异的最主要原因。企业在生产过程中以及检验人员在检验过程中均可造成样品的混合不均匀。

Objective:To discuss examining carefully those factors which might affect the accuracy of the HPLC assay of cefradine/arginine for injection.Methods:Using the HPLC assay method from China Pharmacopoeia and the HPCE method,we determined the content of cefradine and the arginine of cefradine/arginine for injection (two batches) which were applied for arbitration,respectively.Meanwhile,we examined those factors,including content of cefraidine and arginine,filling content,stability,hygroscopy and the test solution preparation might have impact on the accuracy of the assay results.Results:Since cefradine for injection is a compound product,the content uniformity of cefradine and arginine for the final products had a significant impact on the accuracy of the cefradine content value assayed.The results were obvious difference for each test because the different physical characteristic between cefradine and arginine powder.The range between the maximum and minimum assay results of cefradine for 5 vials was almost 8% with a RSD 3.0%.Conclusion:The root cause of the variation among the assay results of cefradine for injection is the mixing uniformity of cefradine and arginine bulk.Both the manufacturers and the operators who do the assay can change the cefradine and arginine's content ratio which has significant influence on the assay results of the final products during the manufacture and the laboratory assay process.