Separation and Characterization of Process-Related Impurities and Forced Degradation Products of G004, a Novel Sulfonylurea Derivative

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• 作者：Chunyan Hong ; Zhou Qiao ; Yahui Guo ; Jinpei Zhou ; Feng Feng ; Wenyuan Liu…
• 关键词：Forced degradation product ; Related compounds ; Potential hypoglycaemic agent ; Preparative HPLC ; Stability ; indicating method
• 刊名：Chromatographia
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：79
• 期：1-2
• 页码：63-69
• 全文大小：498 KB
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• 作者单位：Chunyan Hong (1)
  Zhou Qiao (1)
  Yahui Guo (2)
  Jinpei Zhou (2)
  Feng Feng (3)
  Wenyuan Liu (1) (4)
  Huibin Zhang (2)
  
  1. Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China
  2. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, China
  3. Department of Natural Medicine Chemistry, China Pharmaceutical University, Nanjing, 210009, China
  4. Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing, 210009, China
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Analytical Chemistry
  Organic Chemistry
  Pharmacy
  Biochemistry
  Plant Sciences
  Measurement Science and Instrumentation
  
• 出版者：Vieweg Verlag
• ISSN：1612-1112

文摘

G004, 1-(4-(2-(4-bromobenzenesulphonamino)ethyl)phenylsuphonyl)-3-(trans-4-methylcyclohexyl) urea, is being developed as a potential hypoglycaemic agent. In this study, a stability-indicating HPLC method for G004 and its impurities was investigated. An isocratic HPLC method was developed with an Inertsil C18 column (250 mm × 4.6 mm, 5 µm) and the mobile phase composed of methanol and 25 mM ammonium acetate (65:35, v/v). The flow rate was 1.0 mL min−1 and the column temperature was set at 30 °C. UV detection was carried out at 233 nm. The method was validated with regard to selectivity, linearity, accuracy, precision, and robustness. The analysis of G004 bulk drugs revealed an impurity which had never been reported in G004. The proposed chemical structure of the impurity was confirmed by synthesis and identified as 1-(4-(2-(4-chlorobenzenesulphonamino)ethyl)phenylsuphonyl)-3-(trans-4-methylcyclohexyl) urea. Moreover, a forced degradation study was carried out under acidic, basic, oxidative, photolytic, and thermal conditions. A major degradation product, which was a new compound, was isolated by preparative HPLC and identified as methyl (4-(2-(4-bromobenzenesulphonamino)ethyl)phenylsuphonyl) carbamate. The degradation mechanism of G004 was also proposed.