Abstract
The electrochemical transfer of quinidine across the H~2~O/1,2‐dichloroethane interface was investigated by cyclic voltammetry, so as to determine its lipophilicity. The formal transfer potential was measured as a function of the pH of the aqueous phase. Both singly and doubly protonated quinidine cations can transfer across the interface, and their formal Gibbs free energies of transfer were observed to be 7.7 and 31.2 kJ mol^−1^, respectively. Between pH 0 and 3, only the doubly charged quinidine was present in the aqueous phase and was observed to transfer. Between pH 3 and 6, the transfer of both cations occurred. The proportion of doubly charged quinidine decreased progressively in this pH range and disappeared completely above pH 6. The overall process was analyzed using a thermodynamic model. The relationship between the various forms of quinidine in both phases and pH was established and found to be in good agreement with the experimental results. With this model, the acid‐base equilibrium constants in the organic phase could be calculated as p__K__~a1o~ = 9.66 ± 0.21 and p__K__~a2o~ = 14.20 ± 0.16 (the subscripts a1o and a2o refer to the first and second dissociation constants). This study illustrates how the partition of ionic species can be taken into account in the determination of lipophilicity and in the description of the passive transfer of organic drugs.