Department of Chemistry, K.J. Somaiya College of Science and Commerce, Vidyavihar (E), Mumbai 400077, India.
J Pharm Biomed Anal. 2010 May 1;52(1):73-8. doi: 10.1016/j.jpba.2009.12.021. Epub 2009 Dec 29.
A major process-related impurity associated with the synthesis of ezetimibe was detected by LC-MS. The isolated impurity was found not to have been previously reported. Based on LC/MS/MS studies and accurate mass data, the structure of that impurity was proposed to be 2-(4-hydroxybenzyl)-N,5-bis-(4-fluorophenyl)-5-hydroxypentanamide. The postulated structure was unambiguously confirmed with the help of the NMR and IR analyses of a synthetically obtained sample. The chemical shift of the labile proton of that new entity was assigned by a 2D-NOESY NMR experiment. A rationalization for the formation of this impurity is provided.
LC-MS 检测到与依泽替米贝合成有关的一个主要工艺相关杂质。分离出的杂质以前未曾报道过。根据 LC/MS/MS 研究和精确质量数据，提出该杂质的结构为 2-(4-羟基苄基)-N,5-双-(4-氟苯基)-5-羟基戊酰胺。通过对合成得到的样品进行 NMR 和 IR 分析，明确证实了该假定结构。通过二维 NOESY NMR 实验对该新化合物中不稳定质子的化学位移进行了分配。对该杂质的形成提供了合理解释。
