表征碳青霉烯类药物稳定性的指针性杂质的确定及其应用

目的: 采用自身降解物质作为定量指标,表征碳青霉烯类药物的降解程度,用以考察此类药物的稳定性和指针性杂质共性。 方法: 以美罗培南、亚胺培南和比阿培南为例,进行加速稳定性试验,寻找具有代表性的指针性杂质,并考察药物自身降解程度与指针性杂质之间的量值关系,用以作为稳定性表征指标。 结果: HPLC法分析得到的美罗培南、亚胺培南和比阿培南主成分含量降低1.0%时的警戒线分别为:187,261,84。通过LC-MS确证指针性杂质结构为开环水解物。 结论: 通过对碳青霉烯类药物稳定性考察,依据指针性杂质表征降解程度。

Objective: Using degradation product as quantitative parameter represents the degree of degradation of carbapenem,which determine the stability and property of finger impurity of this kind of antibiotics. Methods: This study used meropenem,imipenem and biapenem as example,performed accelerated stability test for searching specialty finger impurity and investigation the relation between the degradation of carbapenem and the increase of finger impurity. Results: Achieving the warning line of meropenem,imipenem and biapenem were:187,261 and 84 respectively by HPLC.LC-MS confirm the structure of finger impurity was hydrolysate. Conclusion: Determining the stability of carbapenem and using finger impurity represent the extent of degradation.