锆镁磷脂膜色谱固定相的制备及其在评价药物-膜相互作用中的应用

基于锆基质与磷脂之间强烈的路易斯酸碱作用,制备了锆镁磷脂膜色谱固定相,并使用红外光谱、X射线光电子能谱对该色谱固定相进行了表征;使用与体内环境类似的生理缓冲液体系为流动相,评价了该模拟生物膜色谱固定相预测药物膜渗透性的能力,结果表明药物在锆镁磷脂膜色谱中的保留(log Kmbm)与表观渗透率(log Papp)在预测药物的膜渗透性、跨膜吸收等方面具有非常好的相关性,相关系数为0.970,斜率接近1。通过理论推导,引入了直观、方便的热力学指标吉布斯自由能差值（Δ(ΔG°)）对药物-膜之间的相互作用强弱进行了评价。

Preparation of magnesia-zirconia based mimetic biomembrane stationary phase and its applications in evaluating drug-membrane interactions

A novel mimetic biomembrane chromatographic stationary phase of magnesia-zirconia composite matrix was prepared based on the Lewis acid-base interaction between the phosphonate group of phosphatidylcholine residue and the Lewis acid sites of magnesia-zirconia composite. The infrared absorption spectrum and X-ray photoelectron spectrum of the stationary phase illustrated that the magnesia-zirconia composite was successfully modified with phosphatidylcholine. The interactions between the membrane and the drugs were evaluated. It is observed that the log K_mbm values have good relationships with the log P_app, and the linear slope is 1.049, which is near unity. Moreover, on the basis of the thermodynamics derivation, the difference in standard free energies (Δ(ΔG°)) is introduced to describe the drug-membrane interaction. The results show that the log K_mbm and Δ(ΔG°) value provide key information on the transport properties of the drugs. The establishment of this chromatographic model may be a new way for the evaluation of the drug-membrane interactions.