Department of Chemistry, K. J. Somaiya College of Science and Commerce, Vidyavihar (E), Mumbai 400077, India.
J Pharm Biomed Anal. 2011 Sep 10;56(2):256-63. doi: 10.1016/j.jpba.2011.05.024. Epub 2011 May 20.
Four impurities were detected in candesartan cilexetil bulk drug samples by HPLC and LC/MS. These impurities were marked as CDC-I, II, III and IV. One of the impurities CDC-II was unknown and has not been reported previously. An optimized method using liquid chromatography coupled with electrospray ionization ion trap mass spectrometry (LC/ESI-ITMS) in positive ion mode has been developed to carry out structural identification of unknown impurity. Based on mass spectrometric data and synthetic specifics the structure of CDC-II was proposed as 2-ethoxy-1-[[2'-(1-ethyl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid ethyl ester. The impurity was isolated by semi-preparative HPLC and structure was confirmed by NMR spectroscopy. The plausible mechanism for the formation of impurities is also discussed.
高效液相色谱法和液质联用技术检测到坎地沙坦西酯原料药中的 4 种杂质，分别标记为 CDC-I、II、III 和 IV。其中杂质 CDC-II 为未知杂质，此前尚未有报道。采用优化后的方法，以正离子模式的液相色谱-电喷雾离子阱质谱联用技术（LC/ESI-ITMS）对未知杂质进行结构鉴定。根据质谱数据和合成特点，推测出 CDC-II 的结构为 2-乙氧基-1-[[2'-(1-乙基-1H-四唑-5-基)联苯-4-基]甲基]-1H-苯并咪唑-7-羧酸乙酯。该杂质通过半制备高效液相色谱法进行分离，并通过核磁共振波谱法确认了其结构。还讨论了杂质形成的可能机制。
