SolubilityPhysicochemistry and Binding
Only the dissolved fraction of a compound can move through membranes by diffusion or via transporter mechanisms or interact with receptors/enzymes. Solubility is an important parameter in drug development as it is limiting factor for the free-to-interact fraction of the compound in the gastrointestinal fluids, plasma and other matrices in the body.
The solubility of a study compound is determined using either the traditional “shake-flask” –method (thermodynamic solubility) or by spiking DMSO-stock solution into buffer-system (“kinetic” solubility) to minimise the consumption of the study compound. The samples will be filtrated and analysed by LC/PDA/MS.
Physicochemical parameters, such as solubility, are used not only for the prediction of the compounds' behaviour in vivo, but also planning reliable test conditions for other in vitro assays, and therefore it is important to evaluate solubility in the early stage of drug discovery.