UPLC/MS比较分析达托霉素和内酯水解物的酸降解产物

Comparative analysis on acid degradation products of daptomycin and its lactone hydrolysate by UPLC/MS

达托霉素是一种正在临床使用的新型抗耐药菌抗生素。但是由于其结构特点,达托霉素容易受酸碱影响产生降解。本文利用UPLC/MS比较分析了达托霉素及其内酯水解物酸降解后的产物,发现达托霉素主要的降解产物为天冬氨酰-丙氨酰内酰胺键断裂产物,内酯水解物酸的主要降解产物为分子量974的七肽和分子量1160的九肽。通过比较,确定分子量974的有关物质主要来源于内酯水解物的酸降解。并且通过核磁共振检测,确定了该七肽物质的化学结构和氨基酸连接顺序。

Daptomycin is a new anti-resistant antibiotic used in clinic. Due to its structural characteristics, it is easy to be degraded in acid or alkaline conditions. In this study, we used UPLC/MS to compare and analyze the acid degradation products of daptomycin and its lactone hydrolysate, respectively, and found that the main degradation products of daptomycin was aspartyl-alanylamide bond breaking product. The main degradation products of lactone hydrolysate were heptapeptides with molecular weight of 974 and nonapeptides with molecular weight of 1160.Through comparison, we also determined that the related substances with molecular weight of 974 mainly came from acid degradation of lactone hydrolysates. The chemical structure and amino acid sequence of the heptapeptide were determined by NMR.