Kinetics and Thermodynamics of Lactose Mutarotation through Chromatography

The mutarotation kinetics and thermodynamics of the reaction α-lactose ⇌ β-lactose have been measured in dilute solutions using liquid chromatography without any derivatization step, using a C18 column and pure water as the mobile phase. The effect of temperature (0.5-45 °C) of the starting powder composition (α-lactose-rich or β-lactose-rich powder) and of the solvent composition (water with up to 35% weight fraction of seven organic solvents) has been experimentally investigated. Increasing the temperature leads to faster kinetics, following an Arrhenius model, and to slightly decreasing concentration-based equilibrium ratio. Conversely, increasing the weight fraction of organic solvent at 25 °C resulted in slower kinetics and smaller concentration-based equilibrium ratio. The starting powder composition is shown not to influence the kinetics or thermodynamics of the process. The corresponding parameter estimation problem is thoroughly discussed, taking into account the small difference in response factors of the lactose diastereomers.