Separation of Twelve Posaconazole Related Stereoisomers by Multiple Heart-cutting Chiral-chiral Two-Dimensional Liquid Chromatography
Separation of Twelve Posaconazole Related Stereoisomers by Multiple Heart-cutting Chiral-chiral Two-Dimensional Liquid Chromatography
复制标题
多重中心切割手性-手性二维液相色谱分离十二种泊沙康唑相关立体异构体
DOI：
10.1016/j.chroma.2019.460845
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发表时间：
2020
影响因子：
4.1
通讯作者：
Jingwu Kang
中科院分区：
文献类型：
--
作者：
Feng Xu;Yao Xu;Guizheng Liu;Meng Zhang;Shangshang Qiang;Jingwu Kang
泊沙康唑是一种三唑类抗真菌药物，用于治疗各种真菌感染。它有四个手性中心，有16个立体异构体。在聚合合成路线下，活性药物成分（API）中可能只存在11种相关的立体异构体杂质。一次分离所有的立体异构体是一个挑战。为了解决这一问题，建立了一种多重切割心脏的手性-手性二维液相色谱（2D-LC）方法。采用三根手性色谱柱，固定化多糖手性固定相Chiralpak IB、IC和IF3，在2D-LC体系上进行多心切割2D-LC分离。系统采用Chiralpak IB柱作为1d分离柱，IC柱和IF3柱并行进行2d分离。采用多重切心手性-手性2D-LC系统对12种立体异构体进行了一次分离。
Posaconazole represents a triazole antifungal agent which is used to treat various fungal infections. It contains four chiral centers leading to 16 stereoisomers. With the convergent synthesis route, only 11 related stereoisomeric impurities may potentially exist in the active pharmaceutical ingredient (API). It is a challenge to separate all the stereoisomers in one run. To address this problem, a multiple heart-cutting chiral–chiral two-dimensional liquid chromatography (2D-LC) method was developed. The multiple heart-cutting 2D-LC separation was implemented on 2D-LC system with three chiral columns with immobilized polysaccharide chiral stationary phases, namely Chiralpak IB, IC and IF3. In the system, the column Chiralpak IB was used as the1D separation column and IC and IF3 columns were used parallelly for the2D separation. The twelve stereoisomers were all well separated in one run by the multiple heart-cutting chiral–chiral 2D-LC system.