摘要
目的通过测定不同来源的硫辛酸注射液中的顶空残氧量和溶解氧量以及有关物质和主成分的含量,分析数据变化趋势,为硫辛酸注射液的质量控制提供技术参考。方法以原研制剂、自研3批不同溶氧量与残氧量的样品以及市售不同厂家样品为试验对象,采用高效液相色谱法测定不同样品的有关物质[杂质A(6,8-上硫辛烷酸)、杂质B(氧化杂质)、杂质C(降解杂质)]、含量和聚合物,X-325i顶空残氧/溶氧分析仪测定溶氧量与残氧量,进行高温、光照、低温、冻融循环等影响因素试验,以及加速试验、长期试验考察稳定性。结果较高溶氧残氧产品在高温条件下杂质B、C和杂质总量增长趋势明显;光照无外包装条件下,样品中溶氧量与残氧量均显著降低,杂质A和聚合物增长显著;光照带外包装条件下各样品均稳定;低温条件下各样品均稳定;冻融条件下低溶氧量样品不受影响,高溶氧量样品聚合物增加明显;加速条件下,所有自研制剂样品中杂质B和C增加趋势明显,所有样品中溶氧量呈下降趋势,残氧量基本无变化;长期条件下,高溶氧残氧样品杂质C和聚合物有增长趋势。结论越低的氧含量越有利于质量控制,建议在中间产品中控制溶解氧<2μg/mL,残氧量<2.0%,产品较稳定。
Objective To investigate the effects of different dissolved oxygen and residual oxygen on the quality of Thioctic Acid Injection, and to provide technical reference for Thioctic Acid Injection in order to improve the quality. Methods The original preparation, three batches of self-prepared samples with different dissolved oxygen content and residual oxygen content and samples from different manufacturers in the market were used as the test objects. HPLC methods was applied to measure impurities including impurity A(6,8-sulfooctanoic acid), impurity B(oxidation impurity), impurity C(degradation impurity), content and polymer. The dissolved oxygen and residual oxygen were measured by X-325i headspace residual oxygen/dissolved oxygen analyzer. The influence factors test of high temperature, light, low temperature, freeze-thaw cycle, accelerated test and long-term test were carried out to investigate the stability. Results Content of impurities B, C and total amount of impurities increased obviously under high temperature conditions. The dissolved oxygen and residual oxygen in the samples were significantly reduced under the condition of light without outer packaging, and the impurities A and polymer increased significantly. All samples were stable under the light band packaging conditions. All samples were stable under low temperature conditions. The samples with low dissolved oxygen content were not affected under freeze-thaw conditions, but the polymer in the sample with high dissolved oxygen content increases significantly. Under accelerated conditions, impurities B and C in all self-developed preparation samples increased significantly,dissolved oxygen content decreased, and residual oxygen basically remained unchanged in all sample;under long-term conditions,impurity C and polymer in high dissolved oxygen and residual oxygen samples had an increasing trend. Conclusion The lower the oxygen, the better the quality. It is recommended that dissolved oxygen is below 2 μg/mL and residual oxygen is below 2.0%, which the product is stable.
作者
井链
刘莉
陆赛花
周自桂
秦勇
JING Lian;LIU Li;LU Saihua;ZHOU Zigui;QIN Yong(School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210046,China;Burning Point(Nanjing)Biopharm.Co.,Ltd,Nanjing 210046,China)
出处
《药物评价研究》
CAS
2020年第11期2222-2228,共7页
Drug Evaluation Research
