Chromatographic approach for determining the relative membrane permeability of drugs

With the aid of the experimental dependence of the theoretical plate height (H) on the flow-rate (U), values of diffusion coefficients as the permeation rate, of the compounds in a polymeric stationary phase were calculated from solute mass transfer. This approach is proposed for modeling the relative diffusion rate of a drug within the membrane. After the successful separation of opioid compounds using a C18 derivatized polystyrene–divinylbenzene polymer HPLC column, the slopes of H–U plots increase quantitatively in the order of meperidine<alfentanil<fentanyl<sufentanil, indicating that the large mass transfer resistance slows down the penetration of molecules. A constant intercept for the experimental plate height supports the proposal interpretation. A good correlation between the diffusion coefficients and hydrophobicity (log Poct) from the traditional shake-flask method was obtained for the opioid compounds, demonstrating that the more lipophilic molecules penetrate deeper into the stationary phase leading to a lower migration rate under the specified conditions. Plot of the diffusion coefficients versus potency ratio for different opioids after intravenous administration reflect the values of the dynamic process in drug studies. The work herein differs from existing studies by measuring the permeability of drugs into the stationary phase rather than providing membrane partition coefficients for a series of analogues. Thus, the study of drug permeability combined with other physico-chemical properties, such as hydrophobicity, may provide additional information on drug–membrane interactions.