利福拉齐杂质的分析研究

Analysis of Impurities in Rifalazil

目的对利福拉齐的杂质进行分析研究。方法 HPLC对利福拉齐样品进行有关物质检查;TLC检测药品中残留侧链异丁基哌嗪;采用制备TLC、柱色谱法等分离手段对杂质进行分离纯化;HPLC结合TLC及UV、MS、NMR等分析手段对各杂质进行结构推测。结果侧链异丁基哌嗪残留含量低于0.05%;杂质IM-1推测为2-氨基-3-叔丁基二甲基硅氧苯酚;杂质IM-2推测为25-去乙酰基-27-去甲氧基-利福拉齐;杂质IM-3推测为25-去乙酰基利福拉齐;杂质IM-4推测为利福拉齐的29位碳和15位碳断裂的副产物。结论利福拉齐杂质的分析研究对利福拉齐的生产工艺改进具有重要意义。

OBJECTIVE To analyze the impurities of rifalazil.METHODS HPLC method was used for related substances,TLC was used to detect the side chain isobutyl piperazine residues,TLC was prepared and column chromatography was used to separate impurities; HPLC was combined with TLC and UV,MS,NMR and other analytical tools was used to speculate the impurity.RESULTS Impurity IM-1 was to be 2-amino-3-（tert-butyldimethylsilyloxy） phenol,impurity IM-2 was to be 25-deacetyl-27-demethoxy rifalazil,impurity IM-3 was to be 25-deacetyl-rifalazil,IM-4 was to be rifalazil byproduct of 29 carbon and 15 carbon fracture.CONCLUSION The analysis of impurities in rifalazil products has important significance for the improvement of the production process of rifalazil.