Preparative enantioseparation of β-blocker drugs by counter-current chromatography using dialkyl L-tartrate as chiral selector based on borate coordination complex
Preparative enantioseparation of β-blocker drugs by counter-current chromatography using dialkyl L-tartrate as chiral selector based on borate coordination complex
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DOI：
10.1016/j.chroma.2012.09.023
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发表时间：
2012-11-09
影响因子：
4.1
通讯作者：
Lei, Wenyu
中科院分区：
文献类型：
--
作者：
Tong, Shengqiang;Zheng, Ye;Lei, Wenyu
采用逆流色谱技术对心得安、吲哚洛尔和阿普洛尔三种β-受体阻滞剂药物进行了手性拆分。两相溶剂体系为氯仿-0.05mol L-1醋酸酯缓冲液，含0.10mol L-1硼酸(1：1，v/v)，有机相中加入0.10mol L-1酒石酸二己酯作为手性选择剂。考察了普萘洛尔对映体拆分的影响因素。提出了基于硼酸盐配位络合物的色谱保留机理。用高速高效毛细管电泳法一次分离外消旋心得安116 mg，得到(+)-心得安48 mg，HPLC纯度98.9%；(-)-心得安47 mg，HPLC纯度96.3%。普萘洛尔对映体的回收率在75-82%之间。还成功地将pH区精制CCC用于心得安的拆分，发现356 mg的外消旋心得安可以完全拆分。PH区精制得到145 mg的(+)-对映体和148 mg的(-)-对映体，其纯度分别为95.6%和98.2%。探讨了pH区精制CCC手性拆分的分离机理。(C)2012爱思唯尔B.V.保留所有权利。
Counter-current chromatography (CCC) was applied for preparative enantioseparation of three beta-blocker drugs, including propranolol, pindolol and alprenolol. The two-phase solvent system was composed of chloroform-0.05 mol L-1 acetate buffer containing 0.10 mol L-1 boricacid (1:1, v/v), in which 0.10 mol L-1 di-n-hexyl L-tartrate was added in the organic phase as chiral selector. Influence factors in the enantioseparation of propranolol were investigated. The chromatographic retention mechanism based on borate coordination complex was proposed. 116 mg of racemic propranolol was completely enantioseparated using conventional high speed CCC in a single run, yielding 48 mg of (+)-propranolol with HPLC purity of 98.9% and 47 mg of (-)-propranolol with HPLC purity of 96.3%. Recovery for propranolol enantiomers from CCC fractions was in the range of 75-82%. pH-zone-refining CCC was also successfully applied in enantioseparation of propanolol and it was found that 356 mg of racemic propranolol could be completely enantioseparated. 145 mg of (+)-enantiomer with HPLC purity of 95.6% and 148 mg of (-)-enantiomer with HPLC purity of 98.2% were recovered from pH-zone-refining mode. Separation mechanism about chiral separation by pH-zone-refining CCC was discussed. (C) 2012 Elsevier B.V. All rights reserved.