Journal of Chromatography A, 1217 (2010) 1320–1331 Contents lists available at ScienceDirect Journal of Chromatography A journal homepage: www.elsevier.com/locate/chroma On the enantioselectivity of the mass transfer kinetics and the adsorption equilibrium of Naproxen on the chiral stationary phase (R, R)-Whelk-O1 under reversed-phase conditions Leonid Asnin a,b , Krisztián Horváth b,c , Georges Guiochon b,∗ a Institute of Technical Chemistry, The Ural Branch, of the Russian Academy of Sciences, Perm 614013, Russia b Department of Chemistry, University of Tennessee, Knoxville, TN 37996-1600, USA c Department of Analytical Chemistry, University of Pannonia, P.O. Box 158, Veszprém H-8200, Hungary article info Article history: Received 13 October 2009 Received in revised form 16 December 2009 Accepted 21 December 2009 Available online 4 January 2010 Keywords: Chiral separations Naproxen Whelk-O1 Pirkle phases abstract The adsorption of the Naproxen enantiomers on a Pirkle-type chiral stationary phase (CSP) (R, R)- Whelk-O1 from 0.01 M acetic acid solution in a methanol–water (85/15, v/v) mixture was studied using techniques of frontal analysis and elution chromatography. Adsorption was found to follow a model that assumes retention of a solute on two types of surface sites, enantioselective and nonselective. Some minor deviations from the classical bi-Langmuir model were found, but they were well accounted for by assuming the coexistence of two groups of enantioselective sites: sparse sites of strong affinity toward (R)-Naproxen and a more numerous type of low-energy sites exhibiting a somewhat different affinity toward the two enantiomers. Special consideration is paid to the adsorption of the methanol–water mixture on the surface of the CSP. The bonded organic layer exhibits hydrophobic properties, so the adsorbed layer is enriched in methanol throughout the whole range of mobile phase compositions. The study of the mass transfer kinetics was carried out by analyzing the dependence of the HETP on the flow velocity. It revealed the enantioselective character of the intraparticle transport processes. Other aspects of the column dynamics, such as axial dispersion, the external and internal mass transfer were also discussed. © 2009 Elsevier B.V. All rights reserved. 1. Introduction The resolution of the Naproxen enantiomers (Fig. 1) on a Whelk- O1 chiral stationary phase (CSP) (Fig. 2) [1,2] is the most prominent example of direct chromatographic enantioseparation. Since its publication in 1992 [1], it has been abundantly cited in numer- ous reviews and has become an obligatory part of chapters and treatises on chiral separations. It illustrates the potential of chiral chromatography to solve complicated separation problems, like the direct resolution of the racemates of underivatized acids. It is also one of the most successful demonstrations of a rational approach for the design of chiral selectors that has since then become an important tool in the development of CSPs [2]. The nature of the enantiodiscrimination between the Naproxen enantiomers by the Whelk-O1 chiral selector was comprehensively studied [3–9]. However, the macroscopic mechanisms of adsorption of Naproxen ∗ Corresponding author. Fax: +1 865 974 2667. E-mail address: guiochon@utk.edu (G. Guiochon). on this CSP remain unclear. Apparently, only a recent publication [10] discusses the adsorption isotherms of the Naproxen enan- tiomers on this CSP while there are no data on their mass transfer kinetics. The main goal of this work is to fill in the gaps in our knowledge of the equilibrium and the dynamics of adsorption on this important Pirkle-type phase. The work was carried out under reversed-phase conditions (with a methanol–water mobile phase). This choice was dictated by a requirement of a high sol- ubility of the analyte in the mobile phase, which is necessary for the measurement of adsorption isotherms over a wide con- centration range. Besides, the application of Whelk-O1 in the reversed-phase mode has been poorly covered. A few exam- ples of the use of this CSP with water-containing mobile phases have been previously reported [11–13]. The retention of sev- eral chiral analytes in reversed-phase liquid chromatography and in the so-called polar organic mode were studied using a lin- ear chromatography method [14,15]. Therefore the extension of investigations involving aqueous solutions is of separate inter- est. 0021-9673/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.chroma.2009.12.066