Retention Mechanisms for Basic Drugs in the Submicellar and Micellar Reversed-Phase Liquid Chromatographic Modes

Abstract

The reversed-phase liquid chromatographic (RPLC) behavior (retention, elution strength, selectivity, efficiency, and peak asymmetry) for a group of basic drugs (beta-blockers), with mobile phases containing the anionic surfactant sodium dodecyl sulfate (SDS) and acetonitrile, revealed different separation environments, depending on the concentrations of both modifiers: hydro-organic, submicellar at low surfactant concentration and high concentration of organic solvent, micellar, and submicellar at high concentration of both surfactant and organic solvent. In the surfactant-mediated modes, the anionic surfactant layer adsorbed on the stationary phase interacts strongly with the positively charged basic drugs increasing the retention and masks the silanol groups that are the origin of the poor efficiencies and tailing peaks in hydro-organic RPLC with conventional columns. Also, the strong attraction between the cationic solutes and anionic SDS micelles or monomers in the mobile phase enhances the solubility and allows a direct transfer mechanism of the cationic solutes from micelles to the modified stationary phase, which has been extensively described for highly hydrophobic solutes.

Evaluation of Some Empirical Retention Models for High Submicellar Liquid Chromatographic Separation of Aromatic Diamines

“…Recently, Ruiz-Angel et al proposed a mechanistic model to describe the retention behavior of basic drugs (β-blocker) in HSC [13]: which is simplified to: The quadratic and cubic terms in ϕ for the HSC models account for the larger role of the organic solvent in the mobile phase [9,[13][14][15]. The accuracy of eqs.…”

“…It is accepted that micelles are disrupted at concentrations (v/v) above 40% methanol, 30% ethanol, 22% 1-propanol, and 30% acetonitrile [8,9], but these values are not conclusive. However, when the concentration of organic solvent is increased, there is no sudden breakdown of micelles, but a progressive reduction in the aggregation number occurs [10].…”

“…However, when the concentration of organic solvent is increased, there is no sudden breakdown of micelles, but a progressive reduction in the aggregation number occurs [10]. When the added organic solvent induced micelle breakdown, another chromatographic mode has been distinguished in RPLC which was recently called high submicellar chromatography (HSC) by Ruiz-Angel et al [9].…”

“…Consequently, in HSC, only surfactant monomers exist in the mobile phase, which are dissolved in the hydro-organic medium; also, the surfactant coating on the stationary phase is reduced significantly compared to MLC [9,[11][12][13][14][15]. In this mode, ion-pair interactions between charged solutes and free surfactant monomers in the bulk solvent will coexist with the ion exchange on the still surfactant-modified stationary phase [9]. This surfactant-mediated RPLC mode was first used to separate aromatic compounds by Li and Fritz [11] and Jandera et al [12].…”

“…This surfactant-mediated RPLC mode was first used to separate aromatic compounds by Li and Fritz [11] and Jandera et al [12]. Recently, the chromatographic performance of this mode has been perfectly described for a group of basic drugs (β-blockers) [9,[13][14][15], aromatic diamines [16], and some radio-metabolites [17]. The results of these studies showed attractive advantages of HSC with respect to other RPLC modes, in terms of efficiency, peak shape, selectivity, and analysis time.…”