Journal of Chromatography A, 1060 (2004) 195–203 Stationary-phase effects on efficiency in micellar liquid chromatography David P. Thomas a,b , Joe P. Foley a,∗ a Department of Chemistry, Drexel University, 32nd and Chestnut Streets, Philadelphia, PA 19104-2875, USA b Analytical Technical Support, PSGA, A Division of Ortho-McNeil Pharmaceutical, Inc., Titusville, NJ 08560, USA Available online 27 July 2004 Abstract One of the main limitations of micellar liquid chromatography (MLC) is the lower efficiency compared to reversed-phase liquid chromatog- raphy (RPLC) with hydro-organic mobile phases. The main contribution to the reduced efficiency has been shown to be due to the slow mass transfer between micelles, the aqueous phase, and the stationary phase mainly due to surfactant adsorption onto the stationary phase. The use of a variety of stationary phases, including large-pore short alkyl chain, non-porous, superficially porous, and perfluorinated, is shown to have differing effects on remediation of the reduced efficiency. Diffusion coefficients were determined by the Taylor–Aris dispersion technique for the construction of Knox plots. The Knox plots are used to compare the efficiency data obtained with the different columns using several alkylphenones in both micellar mobile phase and hydro-organic mobile phase. © 2004 Elsevier B.V. All rights reserved. Keywords: Micellar liquid chromatography; Efficiency; Diffusion coefficients; Stationary phases, LC; Alkylphenones 1. Introduction Micellar liquid chromatography (MLC) has been plagued by two main problems compared to reversed-phase liquid chromatography (RPLC) with hydro-organic mobile phases: (i) the excessive retention observed for hydrophobic com- pounds due to the weak eluting power of micellar mobile phases when used with conventional porous HPLC station- ary phases [1–6]; and (ii) reduced efficiency due to one or more causes of slower mass transfer and/or flow anisotropy [2–4,7–13]. With respect to excessive retention of hydropho- bic compounds, we recently reported the advantages of us- ing stationary phases with large pore diameter, or “wide-pore stationary phases” in overcoming the perceived weak eluting power associated with micellar mobile phases [14]. We also showed that this wide-pore stationary-phase approach to elut- ing hydrophobic compounds in MLC is compatible with one of MLC’s most important advantages: the direct sample in- troduction of biological fluids [15]. However, the problem of reduced efficiency in MLC still remains [3,4] despite exten- ∗ Corresponding author. Tel.: +1 215 895 6218; fax: +1 215 895 6275. E-mail address: jfoley@drexel.edu (J.P. Foley). sive study [2–4,7–13]. Reduced efficiency in MLC has been attributed to several factors, including (i) poor wetting of the hydrophobic stationary phase by the aqueous mobile phase [2]; (ii) slow mass transfer between the micelles, the bulk aqueous phase, and the stationary phase; and (iii) dynamic modification of the stationary phase due to surfactant ad- sorption [3,4,8,16–23], which further reduces mass transfer within the stationary phase. The contributions to the total peak variance in MLC can be described as follows: σ 2 tot = σ 2 inj + σ 2 det + σ 2 eddy + σ 2 diff,mp + σ 2 diff,sp + σ 2 mt,sp + σ 2 mt(interstitial) + σ 2 mt(intraparticle) (1) where the total peak variance (σ 2 tot ) is the sum of the vari- ances due respectively to sample injection, detection, eddy dispersion (or flow anisotropy), diffusion of the solute in the mobile phase, diffusion of the solute in the stationary phase, stationary-phase mass transfer, mobile-phase mass transfer (between pores or interstitial), and stagnant mobile-phase mass transfer (within the pores, or intraparticle). Based on our previous work with wide-pore station- ary phases, we showed that retention could be greatly 0021-9673/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.chroma.2004.06.043