Identification, separation and characterization of process-related impurities of bifendate derivative (DB-6), an investigational agent combating acute liver failure.

Abstract	DB-6, with an IUPAC name of (Z)-5-(2,4-di-tert-butyl-6-((2,4-dioxothiazolidin-5-ylidene)methyl)phenyl)-5'-methyl-7,7'-dimethoxy-[4,4'-bibenzo[d][1,3]dioxole]-5,5'-dicarboxylate, is an investigational agent for acute liver failure. The focus of this study is the identification and characterization of major unknown impurities in DB-6 bulk drug samples. Four major impurities of DB-6 were detected by a high-performance liquid chromatography (HPLC) method and designated as IMP-I, IMP-II, IMP-III and IMP-IV. Accurate masses of these impurities were determined by using a Q-TOF mass spectrometer. Based on chromatographic, spectrometric data and plausible chemical transformation mechanism, the structures of IMP-I, IMP-II, IMP-III and IMP-IV were identified, respectively, as bifendate, (E)-5-(2,4-di-tert-butyl-6-((2,4-dioxothiazolidin-5-ylidene)methyl)phenyl)-5'-methyl-7,7'-dimethoxy-[4,4'-bibenzo[d][1,3]dioxole]-5,5'-dicarboxylate, (Z)-5-(3,5-di-tert-butyl-2-hydroxybenzylidene) thiazolidine-2,4-dione and bis(2,4-di-tert-butyl-6-((Z)-(2,4-dioxothiazolidin-5-ylidene)methyl)phenyl)-7,7'-dimethoxy-[4,4'-bibenzo[d][1,3]dioxole]-5,5'-icarboxylate. The impurities were isolated by preparative-HPLC or preparative high-speed counter-current chromatography and their structures were confirmed by NMR spectroscopy.
Authors	Weiwei Ye, Yinghong Yang, Guangcheng Wang, Youfu Luo, Lijuan Chen
Journal	Journal of chromatographic science (J Chromatogr Sci) 2015 May-Jun Vol. 53 Issue 5 Pg. 716-24 ISSN: 1945-239X [Electronic] United States
PMID	25238768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].
Chemical References	Biphenyl Compounds Drugs, Investigational bifendate
Topics	Biphenyl Compounds (chemistry, isolation & purification, pharmacology) Chromatography, High Pressure Liquid Drug Contamination Drugs, Investigational (chemistry, isolation & purification, pharmacology) Humans Liver Failure, Acute (drug therapy) Magnetic Resonance Spectroscopy Molecular Structure

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