FI-TRACE Group, Department of Chemistry, University of the Balearic Islands, Carretera de Valldemossa, km 7.5, Palma de Mallorca E-07122, Spain.
CLECEM Group, Department of Analytical Chemistry, University of Valencia, C/Doctor Moliner, 50, Burjassot, Valencia 46100, Spain.
Anal Chem. 2023 Sep 5;95(35):13123-13131. doi: 10.1021/acs.analchem.3c01749. Epub 2023 Aug 24.
There is a quest for a novel in vitro analytical methodology that is properly validated for the prediction of human oral absorption and bioaccumulation of organic compounds with no need of animal models. The traditional log parameter might not serve to predict bioparameters accurately inasmuch as it merely accounts for the hydrophobicity of the compound, but the actual interaction with the components of eukaryotic cells is neglected. This contribution proposes for the first time a novel biomimetic microextraction approach capitalized on immobilized phosphatidylcholine as a plasma membrane surrogate onto organic polymeric sorptive phases for the estimation of human intestinal effective permeability of a number of pharmaceuticals that are also deemed contaminants of emerging concern in environmental settings. A comprehensive exploration of the conformation of the lipid structure onto the surfaces is undertaken so as to discriminate the generation of either lipid monolayers or bilayers or the attachment of lipid nanovesicles. The experimentally obtained biomimetic extraction data is proven to be a superb parameter against other molecular descriptors for the development of reliable prediction models of human jejunum permeability with = 0.76, but the incorporation of log and the number of aromatic rings in multiple linear regression equations enabled improved correlations up to = 0.88. This work is expected to open new avenues for expeditious in vitro screening methods for oral absorption of organic contaminants of emerging concern in human exposomics.
人们一直在寻求一种新型的体外分析方法，该方法经过适当验证，可用于预测有机化合物的人体口服吸收和生物累积，而无需动物模型。传统的 log 参数可能无法准确预测生物参数，因为它仅考虑了化合物的疏水性，但实际上忽略了与真核细胞成分的相互作用。本研究首次提出了一种新型仿生微萃取方法，利用固定化磷脂酰胆碱作为质膜模拟物，结合有机聚合物吸附剂，用于估算多种被认为是环境中新兴关注污染物的药物的人体肠道有效渗透率。对脂质结构在表面上的构象进行了全面的探索，以区分单层或双层脂质的生成或脂质纳米囊泡的附着。实验获得的仿生萃取数据被证明是一种出色的参数，可以替代其他分子描述符，用于开发可靠的人体空肠通透性预测模型， = 0.76，但在多元线性回归方程中加入 log 和芳香环数可将相关性提高至 = 0.88。这项工作有望为人体暴露组学中新兴关注的有机污染物的口服吸收的快速体外筛选方法开辟新的途径。
