title: Isolation, identification and structure elucidation of two novel process-related impurities of retigabine.
abstract: Retigabine was the first neuronal potassium channel opener for the treatment of epilepsy. During the manufacture of retigabine, two unknown impurities were present in laboratory batches in the range of 0.05-0.1% based upon HPLC analysis. These unknown impurities were obtained from the enriched reaction mother liquor by column chromatography. The structure of these process-related impurities were elucidated using FT-IR, (1)H NMR, (13)C NMR, 2D NMR (HSQC, HMBC, NOESY) and MS spectral data. Based on the complete spectral analysis and knowledge of the synthetic route of retigabine, these two new impurities were designated as ethyl 4-fluorobenzyl(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)carbamate (impurity-II) and diethyl 5-((ethoxycarbonyl)(4-fluorobenzyl)amino)-2-oxo-1H-benzo[d]imidazole-1,3(2H)-dicarboxylate (impurity-III). Impurity identification, structure elucidation and the formation of impurities were also discussed.
authors.affiliation: Department of Pharmacy, Food and Pharmaceutical Engineering College, Hubei University of Technology, Wuhan, Hubei 430068, China.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Food and Pharmaceutical Engineering College, Hubei University of Technology, Wuhan, Hubei 430068, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Pharmacy, Food and Pharmaceutical Engineering College, Hubei University of Technology, Wuhan, Hubei 430068, China. Electronic address: jiangtsu@126.com.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Su
mesh_terms: D000927:Anticonvulsants / Q000032:analysis / Q000592:standards*; D002219:Carbamates / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification* / Q000592:standards*; D002264:Carboxylic Acids / Q000737:chemistry / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D007093:Imidazoles / Q000737:chemistry / Q000302:isolation & purification*; D008968:Molecular Conformation; D010655:Phenylenediamines / Q000032:analysis / Q000592:standards*; D021241:Spectrometry, Mass, Electrospray Ionization; D013678:Technology, Pharmaceutical / Q000592:standards*
chemical_list: C000596612:5-((4-fluorobenzyl)amino)-1H-benzo(d)imidazol-2(3H)-one; D000927:Anticonvulsants; D002219:Carbamates; D002264:Carboxylic Acids; D007093:Imidazoles; D010655:Phenylenediamines; C000596611:diethyl 5-((ethoxycarbonyl)(4-fluorobenzyl)amino)-2-oxo-1H-benzo(d)imidazole-1,3(2H)-dicarboxylate; C000596610:ethyl 4-fluorobenzyl(2-oxo-2,3-dihydro-1H-benzo(d)imidazol-5-yl)carbamate; C101866:ezogabine
keywords: Characterization; Identification; Impurity; Isolation; Retigabine