硅醚化制备克拉霉素中相关杂质的色谱分离与检验
Chromatographic Separation and Identification of Related Impurities in Preparation of Clarithromycin through Reaction of Silyl-Etherification
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摘要: 目的分离和确证硅醚化法制备克拉霉素的相关杂质。方法先用TLC找杂质分离条件,再用柱色谱分离提纯,建立HPLC分析方法,以1H-NMR和MALDI-TOF-MS确证结构。结果用色谱和波谱得到并确证了相关杂质分别为4″-O-三甲基硅红霉素A肟(4)和4″-O-三甲基硅红霉素A9(O-叔丁基二甲基硅)肟(5)。结论色谱方法适合于克拉霉素制备中的硅醚化监控。Abstract: OBJECTIVE Separation and identification of related impurities in preparation of clarithromycin through reaction of silyl-etherification.METHODSThe separation condition of impurities was optimized by TLC at first,Separation and purification of the related impurities were conducted by column chromatograph.HPLC chromatograph condition was established.The related impurities in the silyl-etherification were idertified by using 1H-NMR and MALDI-TOF-MS. RESULTSThe related impurities were confirmed as 4"-O-trimethylsilyl erythromycin A oxime (4) and 4"-O-trimethylsilyl erythromycin A 9(o-t-butyldimethylsilyl) oxime (5) by chromatography and spectroscopy. CONCLUSIONThe method could efficiently controll and monitor the quality of clarithromycin preparation in the silyl-etherification procedure.
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