In the present study, 88 structurally- diverse drugs were investigated by biopartitioning micellar chromatography (BMC) using Brij-35 as surfactant under different chromatographic conditions. It was found that temperature and presence of NaCl have only a minor effect in BMC retention. Correlation of BMC retention factors with octanol-water partitioning required the inclusion of fractions of ionized species as additional parameters, showing that there is a weaker effect of ionization in BMC environment. Compared to Immobilized Artificial Membrane (IAM) Chromatography, BMC retention factors cover a relatively narrow span, two-fold smaller than retention factors on IAM stationary phases as a result of the presence of micelles facilitating elution of lipophilic compounds and the absence of secondary attractive electrostatic interactions in the BMC environment. Similarities/dissimilarities between BMC, octanol-water partitioning and IAM Chromatography were investigated by Linear Free Energy Relationships (LSER). BMC retention factors were used to construct relationships with cell permeability,% Human Oral Absorption (%HOA) and Plasma Protein Binding (%PPB). Linear BMC models were obtained with Caco-2 cell lines and Parallel Artificial Membrane Permeability Assay (PAMPA). For %HOA, a hyperbolic model was established upon incorporation of topological polar surface area (tPSA) as additional parameter. A sigmoidal model was constructed for %PPB and a linear one for the corresponding thermodynamic binding constant logK. In both cases inclusion of the fraction of anionic species with a positive sign was required reflecting the preference of human albumin for acidic drugs.

中文翻译：

---

在不同条件下进行生物分配胶束色谱：洞察保留机制和模拟生物过程的潜力。

在本研究中，通过使用Brij-35作为表面活性剂的生物分配胶束色谱（BMC）在不同色谱条件下研究了88种结构多样的药物。发现温度和NaCl的存在对BMC保留仅具有较小的影响。BMC保留因子与辛醇-水分配的相关性要求包含电离物质的馏分作为附加参数，这表明BMC环境中电离作用较弱。与固定化人工膜（IAM）色谱相比，BMC保留因子的覆盖范围相对较小，由于胶束的存在促进了亲脂性化合物的洗脱，并且在BMC环境中不存在次级吸引静电相互作用，因此IAM固定相的保留因子要比保留因子小2倍。通过线性自由能关系（LSER）研究了BMC，辛醇-水分配和IAM色谱之间的异同。BMC保留因子用于构建与细胞通透性，人类口服吸收率（％HOA）和血浆蛋白结合（％PPB）的关系。使用Caco-2细胞系和平行人工膜通透性测定（PAMPA）获得线性BMC模型。对于％HOA，在引入拓扑极性表面积（tPSA）作为附加参数的情况下建立了双曲模型。针对％PPB构造了一个S型模型，对于相应的热力学结合常数logK构造了一个S型模型。在这两种情况下，都需要包含具有正号的阴离子物质部分，以反映人白蛋白对酸性药物的偏爱。