When a compound has limited solubility in water it is common practice (in the pharmaceutical industry, for example) to determine pK values in a solvent mixture such as water/dioxane or water/methanol, in which the compound is more soluble. In the example shown at the right, the pK value rises steeply with increasing percentage of dioxane as the dielectric constant of the mixture is decreasing.
A pK value obtained in a mixed solvent cannot be used directly for aqueous solutions. The reason for this is that when the solvent is in its standard state its activity is defined as one. For example, the standard state of water:dioxane mixture with 9:1 mixing ratio is precisely that solvent mixture, with no added solutes. To obtain the pK value for use with aqueous solutions it has to be extrapolated to zero co-solvent concentration from values obtained from various co-solvent mixtures.
These facts are obscured by the omission of the solvent from the expression that is normally used to define pK, but pK values obtained in a given mixed solvent can be compared to each other, giving relative acid strengths. The same is true of pK values obtained in a particular non-aqueous solvent such a DMSO.
A universal, solvent-independent, scale for acid dissociation constants has not been developed, since there is no known way to compare the standard states of two different solvents.