College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
J Pharm Biomed Anal. 2012 Dec;71:148-51. doi: 10.1016/j.jpba.2012.07.035. Epub 2012 Aug 21.
HPLC analysis of retigabine, a novel antiepileptic drug revealed four previously unknown impurities. These were identified by liquid chromatography-tandem mass spectrometry using electrospray ionization and quadrupole time-of-flight mass analyzer. Further, the structures of the impurities were confirmed by synthesis followed by characterization by mass spectrometry, nuclear magnetic resonance spectroscopy, infrared spectroscopy, and chromatographic retention time profile analysis. On the basis of these data and knowledge of the synthetic scheme of retigabine, the four impurities were identified as ethyl 2,4-diaminophenylcarbamate (Imp-1), ethyl 2-amino-4-(benzylamino)phenylcarbamate (Imp-2), ethyl 2-acetamido-4-(4-fluorobenzylamino)phenylcarbamate (Imp-3), and ethyl 4-(4-fluorobenzylamino)-2-nitrophenylcarbamate (Imp-4). The possible mechanisms by which these impurities were formed are also discussed.
高效液相色谱法分析瑞替加滨，一种新型抗癫痫药物，发现了四种以前未知的杂质。这些杂质是通过电喷雾电离和四极杆飞行时间质谱联用仪的液相色谱-串联质谱法鉴定的。此外，通过合成并进一步通过质谱、核磁共振波谱、红外光谱和色谱保留时间谱分析对杂质的结构进行了确认。基于这些数据以及瑞替加滨的合成方案知识，确定了这四种杂质为乙基 2,4-二氨基苯甲酰胺（杂质 1）、乙基 2-氨基-4-（苄基氨基）苯甲酰胺（杂质 2）、乙基 2-乙酰胺基-4-（4-氟苄基氨基）苯甲酰胺（杂质 3）和乙基 4-（4-氟苄基氨基）-2-硝基苯甲酰胺（杂质 4）。还讨论了这些杂质形成的可能机制。
