盐酸苯达莫司汀有关物质结构鉴定

Identification of the related substances in bendamustine hydrochloride

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（ IMPO1 and IMP02） were detected. These two related substances were identified by LC-MS/MS and their structural confirmation was unam- biguously 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-lH-benzo[ d] imid- azol-2-yl） butyric acid hydrochloride and 4-{ 1-methyl-5-[ （2-chloroethyl） （2-hydroxyethyl） amino] -1H-benzol 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.