艾地骨化醇强制降解试验降解产物的合成  

Synthesis of Degradation Products from the Forced Degradation Tests of Eldecalcitol

作　　者：陈阳生 马庆童 邱传龙 刘振玉 王清亭 CHEN Yangsheng;MA Qingtong;QIU Chuanlong;LIU Zhenyu;WANG Qingting(CP Pharmaceutical Qingdao Co.,Ltd.,Qingdao 266426)

机构地区：[1]正大制药(青岛)有限公司,山东青岛266426

出　　处：《中国医药工业杂志》2024年第7期932-939,共8页Chinese Journal of Pharmaceuticals

基　　金：泰山产业领军人才工程项目(tscx 202211121)。

摘　　要：艾地骨化醇原料药在酸性、碱性、氧化、光照和高温条件下进行强制降解试验,生成(1R,2R,3R,5Z,7E)-2-(3-羟基丙氧基)-9,10-开环胆甾-5,7,10(19),24(25)-四烯-1,3-二醇(AD-1)、(1R,2R,3R,5E,6Z,8Z)-2-(3-羟基丙氧基)-9,10-开环胆甾-5(10),6,8(9)-三烯-1,3,25-三醇(AD-2)、(1R,2R,3R,5E,7E)-2-(3-羟基丙氧基)-9,10-开环胆甾-5,7,10(19)-三烯-1,3,25-三醇(AD-3)、(1R,2R,3R,5E,6E,8Z)-2-(3-羟基丙氧基)-9,10-开环胆甾-5(10),6,8(9)-三烯-1,3,25-三醇(AD-4)和(1R,2R,3R,14S,5E,6Z,8Z)-2-(3-羟基丙氧基)-9,10-开环胆甾-5(10),6,8(9)-三烯-1,3,25-三醇(AD-5)这5种降解产物。其中,AD-1和AD-5未见文献报道。该文合成了AD-1和AD-5,并优化了AD-4的合成工艺,产物经1 H NMR、13C NMR和MS结构确证。文章为艾地骨化醇的质量研究提供了一定的参考,同时为其生产、包装、贮存提供了依据。Forced degradation tests of eldecalcitol API were conducted under acidic,alkaline,oxidative,lightexposed,and high-temperature conditions.Five degradation products were generated,namely(1R,2R,3R,5Z,7E)-2-(3-hydroxypropoxy)-9,10-secocholesta-5,7,10(19),24(25)-tetraene-1,3-diol(AD-1),(1R,2R,3R,5E,6Z,8Z)-2-(3-hydroxypropoxy)-9,10-secocholesta-5(10),6,8(9)-triene-1,3,25-triol(AD-2),(1R,2R,3R,5E,7E)-2-(3-hydroxypropoxy)-9,10-secocholesta5,7,10(19)-triene-1,3,25-triol(AD-3),(1R,2R,3R,5E,6E,8Z)-2-(3-hydroxypropoxy)-9,10-secocholesta-5(10),6,8(9)-triene-1,3,25-triol(AD-4)and(1R,2R,3R,14S,5E,6Z,8Z)-2-(3-hydroxypropoxy)-9,10-secocholesta-5(10),6,8(9)-triene1,3,25-triol(AD-5).Among them,AD-1 and AD-5 were not found in literatures.This study developed synthetic routes for AD-1 and AD-5,and optimized the synthesis process for AD-4.The structures of these products were confirmed by 1 H NMR,13C NMR,and MS.This paper provides the references for the quality research of eldecalcitol,as well as its production,packaging,and storage.

关 键 词：艾地骨化醇 降解 合成 质量控制 

分 类 号：R977.2[医药卫生—药品]