Nerissa L. Deñola 1 Noel S. Quiming 1 Alicia P. Catabay 2 Yoshihiro Saito 1 Kiyokatsu Jinno 1 1 School of Materials Science, Toyohashi University of Technology, Toyohashi, Japan 2 Faculty of Pharmacy, Kuwait University, Kuwait Received December 22, 2005 Revised March 9, 2006 Accepted March 10, 2006 Research Article Optimization of capillary electrophoretic enantioseparation for basic drugs with native â-CD as a chiral selector This study presents the advantages of the 20 mm inner diameter (id) capillary for the enantioseparation of ten basic drugs with native b-CD as the chiral selector. The apparent binding constants of each enantiomeric pair were determined to calculate the optimum b-CD concentration ([b-CD] opt ) and the optimization was subsequently car- ried out. Comparison of the 20 mm id with 50 mm id were made in terms of the results obtained in the optimization and detection limits. Applying the optimum conditions for each compound, reproducible results (RSD from 0–3; n.5) were obtained for the 20 mm id capillary. Although the sensitivity is lower in the 20 mm id capillary, the LOD determined using this capillary is still found to be acceptable for the ten basic drugs studied. Enhanced resolution and faster analysis times were the main advantages observed with the use of this capillary in enantioseparation. Keywords: Basic drugs / b-CD / Capillary electrophoresis / Enantioseparation DOI 10.1002/elps.200500943 1 Introduction Enantioseparation by CE has been widely studied in recent years and the principles of chiral separation in CE have been reviewed extensively in several monographs and articles [1–9]. This is largely due to the impact of CE on the pharmaceutical industry. Many compounds of pharmacological interest have one or more centers of asymmetry and usually one of the enantiomers is more active than another, or which might even be inactive or toxic. Currently, many synthetic chiral drugs are marketed as racemates [10] and it is therefore important to develop enantioseparation methods for pharmacological investi- gation of drug quality control. Although other analytical methods such as HPLC [11–13], TLC [14], GC [15, 16], and supercritical fluid chromatog- raphy (SFC) [17] were used for enantioseparation, CE has been established as a very efficient technique for the separation of drug enantiomers because of its high effi- ciency, short analysis time, versatility due to the great variety of chiral selectors that can be added to the BGE, short equilibration times required when changing the chiral selector and low consumption of selectors [18–23]. In CE the separation of chiral compounds is achieved mainly by the direct separation where the chiral selector is simply added to the BGE or bonded to either the capillary wall or to a stationary phase. CDs and their derivatives are the most widely used chiral selectors in CE [1]. Using CDs, analytes fit either completely or with their hydro- phobic part into the CD cavity [24] entering through one of the two openings, primary and secondary with 6-hydroxyl and 2-, 3-hydroxyl groups, respectively [25]. The complex formed during the electrophoretic process, in equilibrium with the free analyte, possesses a different mass respon- sible for the change in effective mobility. It has been established that the enantioresolution can be influenced by several parameters such as the type and concentration of CD, pH and composition of the BGE, capillary temperature, applied voltage, additive to the BGE, etc. [5, 26]. In this study, the effects of smaller cap- illary id to enantioseparation were studied. Uncoated fused-silica capillaries 25–75 mm id are com- monly used in direct enantioseparation. In this study, the use 20 mm id capillary with native b-CD as the chiral selector for the enantioseparation of ten basic drugs Correspondence: Professor Kiyokatsu Jinno, School of Materials Science, Toyohashi University of Technology, Toyohashi 441–8580, Japan E-mail: jinno@chrom.tutms.tut.ac.jp Fax: 181-532-48-5833 Abbreviations: [â-CD] opt , optimum b-CD concentration; TEA, triethylamine Electrophoresis 2006, 27, 2367–2375 2367  2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.electrophoresis-journal.com