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pH-dependent surface electrostatic effects in retention on immobilized artificial membrane chromatography: determination of the intrinsic phospholipid-water sorption coefficients of diverse analytes A
- Yang, Yu-Xiu, Zhang, Qian, Li, Qiao-Qiao, Xia, Zhi-Ning, Chen, Hua, Zhou, Kai, Yang, Feng-Qing
- Journal of chromatography 2018
- anions, cations, chromatography, drugs, electrostatic interactions, ionic strength, ionization, mathematical models, membrane permeability, pH, sorption
- The passive membrane permeability of drugs may be potentially predicted by phospholipid-water sorption coefficient (KPLIPW) through immobilized artificial membrane (IAM) chromatography. However, for predominantly ionized compounds, unexpected confounding electrostatic interaction would influence the accurate determination of KPLIPW, accompanied by the mobile phase with varied pH and ionic strength. In order to measure the intrinsic phospholipid-water sorption coefficient (KIAM,intr) for diverse analytes, a mathematic model by characterizing the confounding electrostatic effects was developed in this study. Based on the developed electrostatic model, additional electrostatic repulsion/attraction interactions with the charged IAM surface were characterized for organic cations/anions. Considering that most of the IAM chromatography data was determined under physiological conditions, the KPLIPW values of all compounds were calculated with the ionic strength of 0.1 M and the pH value of 7. Generally, KPLIPW was hardly affected by the pH and ionic strength of mobile phase for those electroneutral compounds. KIAM,intr was 0.28 log units smaller than apparent phospholipid-water sorption coefficient (KIAM,app) for cations. In contrast, KIAM,intr was larger than KIAM,app by 0.28 log units for anions. Herein, KIAM,intr of diverse analytes can be easily calculated by the developed electrostatic model. For application, KIAM,intr was further compared with intrinsic Caco-2 permeability, and good sigmoidal correlations (R² = 0.76) were established between them for organic cations and neutral compounds but not for organic anions.