Semi-empirical relationships between effective mobility, charge, and molecular weight of pharmaceuticals by pressure-assisted capillary electrophoresis: applications in drug discovery.

Relationships between effective mobility (m e f f ), calculated charge (Z c ), and molecular weight (MW) are semi-empirically derived for pharmaceuticals using pressure-assisted capillary electrophoresis (PACE). We determined the m e f f at 12 different pH points (2.0-11.4) of 66 pharmaceutical-like compounds ranging in MW from 79 to 825 g/mol. Plots of the observed m e f f values versus Z c /MW x (where x is a fractional coefficient) gave linear relationships. For anions, it was found that the best correlation (R 2 = 0.9666) exists when the fractional coefficient is equal to 0.4920, resulting in the equation m e f f = 0.1853 (Z c /MW 0 . 4 9 2 0 ). For cations, the best linear relationship (R 2 = 0.9861) gave the equation m e f f = 0.3888 (Z c /MW 0 . 6 3 3 0 ). The m e f f , Z c /MW x relationships were then applied to: (i) developing a technique for selecting an appropriate pH to achieve optimal separation of pharmaceuticals and (ii) determining the maximum charge of a molecule in the pH range of determination of negative log of the dissociation constants (pK a ) by PACE, thus enabling the correct choice of model equation to be automated without structure analysis.