Tetrad Of Equilibria

The topic of drug partitioning between water and lipids concerns chemical equilibria. For a monoprotic weak acid (and base), the partitioning equilibria may be represented as

As mentioned in Chapater 3, the law of mass action sets the concentration relations of the reactants and products. So, the equilibrium constants, termed the partition coefficients, are the quotients

where [HA] ([B]) is the free-acid (free-base) aqueous concentration, moles/liter aqueous solution, and the ORG-subscripted term is the concentration in the oil phase, moles/liter of organic solvent [347]. When the partition coefficient is determined directly, usually the aqueous concentration is determined analytically (UV or HPLC), and the oil-phase counterpart is inferred through mass balance [245]. Not only the neutral species, but the charged species can partition into the organic phase (such as octanol), although usually to a much lesser extent:


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