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Influence of Solvent Effects on Retention of Small Molecules in Reversed-Phase Liquid Chromatography

Poole, Colin F.
Chromatographia 2019 v.82 no.1 pp. 49-64
Gibbs free energy, adsorption, interphase, mechanistic models, molecular dynamics, reversed-phase liquid chromatography, simulation models, solvents, uncertainty
Major obstacles to formulating a simple retention mechanism for reversed-phase liquid chromatography are identified as the heterogeneous composition of the stationary phase, the difficulty of providing a working definition for the phase ratio, and uncertainty as to whether the distribution mechanism for varied compounds are a partition or adsorption process or some combination of both. Some insight into the retention mechanism is provided by isotherm measurements, studies of surface excess adsorption, and molecular dynamics simulations, while on the other hand, retention factor measurements offer little guidance as they represent an average of various and variable contributing factors that can only be deconvoluted by assuming a specific model. The interphase model offers a phenomenological description of the active region of the stationary phase responsible for retention, but is not connected with any specific mathematical formulation on the retention mechanism. Mechanistic models based on solvophobic theory, lattice theories, and partition displacement models are of limited practical utility because of their complexity and unrealistic assumptions required in most part to simplify the mathematical description of the interphase region. Linear free energy relationships, such as the solvation parameter model, provide a simpler solution offering useful insights into the retention process for column selection and mobile phase optimization. Even here, caution is indicated as the interpretation of solvent effects on system constants implies an understanding of the retention mechanism which remains an enigma in search of a solution.