title: Determination and characterization of two degradant impurities in bendamustine hydrochloride drug product.
abstract: Bendamustine hydrochloride is an alkylating antitumor agent with a good efficacy in the treatment of chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin's lymphoma (B-NHL). Under the stressed conditions, two degradant impurities in bendamustine hydrochloride drug product were detected by high-performance liquid chromatography. These two degradant impurities were isolated from preparative liquid chromatography, and were further characterized using Q-TOF/MS and nuclear magnetic resonance (NMR). Based on the MS and NMR spectral data, they were characterized as 4-[5-(2-chloro-ethylamino)-1-methyl-1H-benzoimidazol-2-yl] butyric acid hydrochloride (impurity-A) and 4-{5-[[2-(4-{5-[bis-(2-chloroethyl) amino]-1-methyl-1H-benzoimidazol-2-yl}-butyryloxy)-ethyl]-(2-chloroethyl)amino]-1-methyl-3a, 7a-dihydro-1H-benzoimidazol-2-yl} butyric acid hydrochloride (impurity-B). Isolation, structural elucidation of these two impurities by spectral data (Q-TOF/MS, (1)H NMR, (13)C NMR, D2O exchange NMR and two-dimensional NMR) and the probable formation mechanism of the impurities were discussed.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Chen
authors.affiliation: Jiangsu Simcere Pharmaceutical Group Ltd, Xuanwu Avenue No. 699-18, Nanjing 210042, PR China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zou
authors.affiliation: Jiangsu Simcere Pharmaceutical Group Ltd, Xuanwu Avenue No. 699-18, Nanjing 210042, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Jiangsu Simcere Pharmaceutical Group Ltd, Xuanwu Avenue No. 699-18, Nanjing 210042, PR China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Jiangsu Simcere Pharmaceutical Group Ltd, Xuanwu Avenue No. 699-18, Nanjing 210042, PR China.
authors.forename: Liandi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Jiangsu Simcere Pharmaceutical Group Ltd, Xuanwu Avenue No. 699-18, Nanjing 210042, PR China.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Liao
authors.affiliation: Jiangsu Simcere Pharmaceutical Group Ltd, Xuanwu Avenue No. 699-18, Nanjing 210042, PR China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China dinglidl@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D000069461:Bendamustine Hydrochloride / Q000737:chemistry*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002851:Chromatography, High Pressure Liquid; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000970:Antineoplastic Agents; D000069461:Bendamustine Hydrochloride