刘文宝,刘岩,游松
LIU Wen-bao1,LIU Yan2,YOU Song1(1.School of Life Science and Biopharmaceutics

• 1:沈阳药科大学生命科学与生物制药学院
• 2:沈阳药科大学药学院

摘要(Abstract)：

目的对氯可托龙新戊酸酯及其原料药中有关物质进行分离及结构鉴定。方法采用制备高效液相色谱法对氯可托龙新戊酸酯中的杂质进行分离,并应用HPLC-ESI-MS、NMR、UV、IR法对氯可托龙新戊酸酯及其有关物质进行结构鉴定。结果氯可托龙新戊酸酯原料药中含有(6R,9R,16R)-9-氯-6β-氟-11β,21-二羟基-16α-甲基-1,4-孕甾二烯-3,20-二酮-21-新戊酸酯[(6R,9R,16R)-9-chloro-6β-fluoro-11β,21-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione-21-pivalate,1]、(9R,16R)-9-氯-4-氟-11β,21-二羟基-16α-甲基-1,4-孕甾二烯-3,20-二酮-21-新戊酸酯[(9R,16R)-9-chloro-4-fluoro-11β,21-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione-21-pivalate,2]和(9R,16R)-9-氯-6α-氟-11β,21-二羟基-16α-甲基-1,4-孕甾二烯-3,20-二酮-11,21-二新戊酸酯[(9R,16R)-9-chloro-6α-fluoro-11β,21-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione-11,21-dipivalate,3]3种杂质。结论从氯可托龙新戊酸酯原料药中分离得到3个杂质,3个化合物均为首次发现。其中杂质1为6-H的差向异构体,杂质2为同分异构体,杂质3为11-OH与新戊酸酯化产物。结合合成过程分析,三者可能均为合成过程中的副产物。
Objective To isolate and identify the structures of clocortolone pivalate and three related substances in its bulk drug.Methods These main impurities were separated using semi-preparative HPLC.The structures of these compounds were identified using HPLC-ESI/MS,NMR,UV and IR.Results Three impurities were isolated and identified as(6R,9R,16R)-9-chloro-6β-fluoro-11β,21-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione-21-pivalate(1),(9R,16R)-9-chloro-4-fluoro-11β,21-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione-21-pivalate(2)and(9R,16R)-9-chloro-6α-fluoro-11β,21-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione-11,21-dipivalate(3),respectively.Conclusions The three related substances are isolated from the bulk drug of clocortolone pivalate,which all have not been reported previously;impurity 1 is the H6 epimer of clocortolone pivalate,impurity 2 is the isomer of clocortolone pivalate and impurity 3 is the esterification product of clocortolone pivalate at 11-OH.Based on the synthesis process,all these impurities are possibly by-products in synthesis process.

关键词(KeyWords)： 氯可托龙新戊酸酯;有关物质;结构鉴定
clocortolone pivalate;related substance;structure identification

Abstract:

Keywords:

基金项目(Foundation): 国家科技重大专项—重大新药创制专项资助项目(2010ZX09401-304)

作者(Author): 刘文宝,刘岩,游松
LIU Wen-bao1,LIU Yan2,YOU Song1(1.School of Life Science and Biopharmaceutics

DOI: 10.14066/j.cnki.cn21-1349/r.2012.10.011

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