盐酸苯达莫司汀有关物质结构鉴定

建立HPLC法对盐酸苯达莫司汀的有关物质进行分析，检测出2个有关物质IMP01和 IMP02；通过LC-MS/MS法推测出2个有关物质的结构，并合成制备得到2个有关物质单体，根据Q-TOF/MS以及NMR结果综合解析确证了两个有关物质结构，IMP01为4-(1-甲基-5-吗啉-2-苯并咪唑基)丁酸盐酸盐，IMP02为4-{1-甲基-5-［(2-氯乙基)(2-羟乙基)氨基］-2-苯并咪唑基}丁酸盐酸盐。结果显示，在建立的LC-MS条件下，盐酸苯达莫司汀与其有关物质分离良好，通过分析鉴定有关物质结构，为其工艺和质量控制提供了参考依据。
In the HPLC analysis of bendamustine hydrochloride, two related substances(IMP01 and IMP02)were detected. These two related substances were identified by LC-MS/MS and their structural confirmation was unambiguously carried out by synthesis followed by characterization using Q-TOF/MS and NMR. Based on the spectral data, related substances IMP01 and IMP02 were characterized as 4-(1-methyl-5-morpholino-1H-benzo［d］imidazol-2-yl)butyric acid hydrochloride and 4-{1-methyl-5-［(2-chloroethyl)(2-hydroxyethyl)amino］-1H-benzo［d］imidazol-2-yl)} butyric acid hydrochloride, respectively. Bendamustine hydrochloride and its related substances were separated under the established LC-MS condition. HPLC is a useful method for the determination of the related substances in bendamustine hydrochloride. Results obtained are valuable for its manufacturing process and quality control