College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
J Pharm Biomed Anal. 2011 Apr 5;54(5):1007-12. doi: 10.1016/j.jpba.2010.12.001. Epub 2010 Dec 10.
The current study demonstrates the reversal of enantiomer migration order (EMO) in capillary electrophoresis (CE) based separations of sibutramines (SIB) as a function of the concentration of two types of cyclodextrin (CD), native β-CD and acetyl-β-CD. At normal working concentrations (<10mM) of either CD, (S)-SIB migrated first. However, at CD concentrations greater than 10mM, (R)-SIB was the first to migrate. This study describes factors involved in determining EMO for sibutramine enantiomers at low and high concentrations of CDs. The reversal of EMO could be explained in terms of the opposing effects of the stability and the limiting complex mobility of the SIB-CD complexes. The enantioseparation of SIB with methyl- and 2-hydroxypropyl-β-CD was possible based on differences in the binding constants of complexes. However, reverse EMO was not observed because of equal mobilities of SIB enantiomers complexed with methyl- and 2-hydroxypropyl-β-CD.
本研究表明,在毛细管电泳(CE)中,舒必利(SIB)对映体迁移顺序(EMO)随两种环糊精(CD)浓度的变化而反转,这两种 CD 分别为天然β-CD 和乙酰-β-CD。在低于 10mM 的 CD 正常工作浓度下,(S)-SIB 先迁移。然而,在 CD 浓度大于 10mM 时,(R)-SIB 先迁移。本研究描述了在 CD 低浓度和高浓度下确定 SIB 对映体 EMO 的相关因素。EMO 的反转可以用 SIB-CD 配合物的稳定性和限制配合物迁移率的相反作用来解释。基于 SIB-CD 配合物结合常数的差异,SIB 可以用甲基-β-CD 和 2-羟丙基-β-CD 进行对映体分离。然而,由于 SIB 对映体与甲基-β-CD 和 2-羟丙基-β-CD 形成的配合物的迁移率相等,因此没有观察到反向 EMO。