缬沙坦胶囊有关物质的检测分析

Analysis of Related Substances in Valsartan Capsules

目的评价缬沙坦胶囊的有关物质现状及存在的问题。方法采用现行标准结合探索性研究对8个厂家的175批样品进行考察,并对结果进行分析。结果采用法定标准检验,174批样品有关物质均符合规定,1批不符合规定,不合格样品检出一个含量为1.0%的未知杂质,杂质总量为1.1%,超出了规定限度(标准规定:单个杂质不得过0.2%,杂质总量不得过0.7%);探索性研究表明,该未知杂质仅在2个厂家的制剂中检出,原料药中未检出该杂质,提示该杂质非工艺杂质,系制剂产生的降解产物;采用LC-MS/MS技术分析推断该杂质结构,结合制剂工艺,明确其产生途径。结论国产缬沙坦胶囊及原料药有关物质控制基本能符合现行标准要求,达到了与原研相当的水平;分析不合格样品超限度杂质的产生原因,反映出个别厂家在制剂工艺的选择及关键质控点的控制上有待改进,以保证产品的稳定性。

OBJECTIVE To evaluate the status of related substances in valsartan capsules and find the existing problems. METHODS One hundred and seventy-five batches of samples from eight manufacturers were tested using statutory methods combined with exploratory research, and the results were evaluated by statistical analysis. RESULTS The related substances in 174 batches of valsartan capsules met the requirement of current specification,while one batch did not. For the batch of substandard sample, the amount of an individual impurity was 1.0% and the total amount was 1.1%, exceeding the corresponding limits of 0. 2% and 0. 7%, respectively. The unknown impurity was detected in samples from two manufacturers in the exploratory studies, but not detected in valsartan API, suggesting that the unknown impurity may be degradation product, rather than process impurity. The structure of the unknown impurity was identified by LC-MS/MS, and the reason for its generation was elucidated through preparation process research. CONCLUSION The related substances in valsartan capsules are in good control overall and have met the requirement of current statutory specification. The individual manufacturer should strengthen process control to ensure the stability of the products by inference of unqualified samples.