Wan Ibrahim Wan Aini, Arsad Siti Rosilah, Maarof Hasmerya, Sanagi Mohd Marsin, Aboul-Enein Hassan Y
Separation Science & Technology Group (SepSTec), Department of Chemistry, Faculty of Science, Sukdai, Johor Bahru, Johor, Malaysia; Nanotechnology Research Alliance, Universiti Teknologi Malaysia, Sukdai, Johor Bahru, Johor, Malaysia; Ibnu Sina Institute for Fundamental Science Studies, Universiti Teknologi Malaysia, Sukdai, Johor Bahru, Johor, Malaysia.
Chirality. 2015 Mar;27(3):223-7. doi: 10.1002/chir.22416. Epub 2014 Dec 18.
This work aimed to develop a chiral separation method of ketoconazole enantiomers using electrokinetic chromatography. The separation was achieved using heptakis (2, 3, 6-tri-O-methyl)-β-cyclodextrin (TMβCD), a commonly used chiral selector (CS), as it is relatively inexpensive and has a low UV absorbance in addition to an anionic surfactant, sodium dodecyl sulfate (SDS). The influence of TMβCD concentration, phosphate buffer concentration, SDS concentration, buffer pH, and applied voltage were investigated. The optimum conditions for chiral separation of ketoconazole was achieved using 10 mM phosphate buffer at pH 2.5 containing 20 mM TMβCD, 5 mM SDS, and 1.0% (v/v) methanol with an applied voltage of 25 kV at 25 °C with a 5-s injection time (hydrodynamic injection). The four ketoconazole stereoisomers were successfully resolved for the first time within 17 min (total analysis time was 28 min including capillary conditioning). The migration time precision of this method was examined to give repeatability and reproducibility with RSDs ≤5.80% (n =3) and RSDs ≤8.88% (n =9), respectively.
本研究旨在开发一种采用电动色谱法分离酮康唑对映体的手性分离方法。使用七（2,3,6-三-O-甲基）-β-环糊精（TMβCD）作为常用的手性选择剂（CS）实现了分离，因为它相对便宜，除了阴离子表面活性剂十二烷基硫酸钠（SDS）外，在紫外光区吸光度较低。研究了TMβCD浓度、磷酸盐缓冲液浓度、SDS浓度、缓冲液pH值和施加电压的影响。在25℃下，采用5 s进样时间（流体动力学进样）、25 kV的施加电压，使用pH 2.5的10 mM磷酸盐缓冲液，其中含有20 mM TMβCD、5 mM SDS和1.0%（v/v）甲醇，实现了酮康唑手性分离的最佳条件。首次在17分钟内成功分离出四种酮康唑立体异构体（包括毛细管平衡在内的总分析时间为28分钟）。该方法的迁移时间精密度经检测具有重复性和重现性，相对标准偏差（RSD）分别≤5.80%（n = 3）和≤8.88%（n = 9）。
