注射用灯盏花素制剂中相关物质的分析与结构鉴定

Analysis and structural identification of relevant substances in Breviscapine for Injection

为了明确注射用灯盏花素制剂的相关物质组成,提升杂质控制水平,保障注射剂的临床用药安全,该研究采用HPLC和UPLC-QTOF/MS对不同规格不同批号注射用灯盏花素制剂进行相关物质分析与鉴定,主要的相关物质为5,6,7,3′,4′-五羟基黄酮-7-O-葡萄糖醛酸苷(3)、3,5,6,7,4′-五羟基黄酮-3-O-葡萄糖醛酸苷(4)和野黄芩素(10);3个极微量的相关物质为6-羟基芹菜素-6-O-葡萄糖-7-O-葡萄糖醛酸苷(1)、甲氧基野黄芩苷(6)和灯盏甲素(7)。采用半制备HPLC对主要相关物质3和4进行了分离纯化,经核磁共振波谱数据分析,进一步确证了它们的结构。该研究明确了注射用灯盏花素制剂的相关物质组成,为提升制剂中单个杂质的控制水平提供参考。

To define the composition of relevant substances in Breviscapine for Injection,in order to improve the quality control of impurity,and ensure the clinical safety.The analysis and structural identification of relevant substances in different specifications and batches of Breviscapine for Injection powders were carried out by HPLC and UPLC-QTOF-MS.Three primary relevant substances,namely 5,6,7,3′,4′-pentahydroxyflavone-7-O-glucuronide(3),3,5,6,7,4′-pentahydroxyflavone-3-O-glucuronide(4)and scutellarein(10),as well as three minor impurities,namely 6-hydroxyapigenin-6-O-glucosyl-7-O-glucuronide(1),methoxylscutellarin(6)and apigenin-7-O-glucuronide(7)were structurally identified by matching retention time,UV spectra,and mass spectra with authentic compounds and MS fragmentation rules.The main relevant substances(3)and(4)were separated and purified by semi-preparative HPLC,and their structures were further confirmed by NMR data.The study defined relevant substances of Breviscapine for Injection,and provided reference for improving the quality control level of single impurity in breviscapine preparation.