克林霉素磷酸酯原料药杂质的分离制备和结构鉴定

Isolation and identification of impurities from raw material of clindamycin phosphate

摘要:
通过制备液相色谱分离克林霉素磷酸酯 (clindamycin phosphate) 原料药中4个杂质, 并利用LC-MS方法、高分辨质谱、核磁共振等方法对杂质进行结构鉴定。4个杂质分别鉴定为克林霉素-B-磷酸酯 (1)、2, 4-克林霉素二磷酸酯 (2)、3', 6'-去氢克林霉素磷酸酯 (3) 和表克林霉素磷酸酯 (4)。杂质1为《英国药典》和《欧洲药典》在可能的杂质的收载项中收载的杂质, 杂质2、3、4均未收载, 为首次从克林霉素磷酸酯原料药中分得。

Abstract:
Four impurities were isolated from raw material of clindamycin phosphate (CP), and their structures have been determined. LC-MS was used to determine the molecular weights of the impurities in the raw material of CP. Reversed-phase preparative HPLC was used to prepare them, and their chemical structures were identified by HR-MS and NMR. The four unknown impurities were determined as clindamycin-B-phosphate (1), clindamycin-2, 4-diphosphate (2), 3', 6'-dehydro clindamycin phosphate (3), epi-clindamycin phosphate (4). Impurity 1 has been included in BP and EP, while 2, 3 and 4 have not. The impurities 2, 3, 4 are first separated from raw material of CP.