A comprehensive two-dimensional liquid chromatography-based biomimetic platform (LCxLC) has been developed and validated for drug diffusion studies. Human serum albumin (HSA) and immobilized artificial membrane (IAM) were thereby used in the first (1D) and second (2D) separation dimension, respectively. While the former was meant to emulate the blood, the latter was instead intended to mimic the intestinal mucosa epithelium. Therefore, the experimental conditions, i.e. pH, temperature and buffer composition, were modulated to reflect faithfully in vivo conditions. 30 compounds, whose effective intestinal permeability (Peff) assayed in situ on humans by a validated technique was known from the literature, were used as model drugs. A good and orthogonal separation was achieved for the whole dataset, although for a better distribution of the most polar compounds in the elution window a segmented gradient elution program had to be employed. Interestingly, the passively uptaken compounds having the most favourable Peff populated a specific area of the 2D plots, implying that the affinity for HSA and IAM has to lie in specific ranges in order for a compound to be satisfactorily absorbed from the intestinal lumen. Although these results should be regarded as preliminary, this work paves an entirely new and unprecedented way to profile pharmaceutically relevant compounds for their in vivo absorption and distribution potential.

中文翻译：

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综合二维液相色谱作为仿生筛选平台，用于早期药物开发中化合物库的药代动力学分析

已经开发并验证了一种基于二维液相色谱的综合仿生平台 (LCxLC)，用于药物扩散研究。因此，人血清白蛋白 (HSA) 和固定化人工膜 (IAM) 分别用于第一 (1D) 和第二 (2D) 分离维度。前者旨在模拟血液，而后者旨在模拟肠粘膜上皮。因此，调节实验条件，即pH、温度和缓冲液组成，以忠实地反映体内条件。30 种化合物用作模型药物，其有效肠道通透性 (Peff) 通过经验证的技术对人体进行原位测定，这些化合物已从文献中获知。整个数据集实现了良好的正交分离，尽管为了使大多数极性化合物在洗脱窗口中更好地分布，必须采用分段梯度洗脱程序。有趣的是，具有最有利 Peff 的被动吸收化合物占据了 2D 图的特定区域，这意味着对 HSA 和 IAM 的亲和力必须位于特定范围内，以便化合物从肠腔中被令人满意地吸收。虽然这些结果应该被视为初步结果，但这项工作为分析药物相关化合物的体内吸收和分布潜力铺平了道路。这意味着对 HSA 和 IAM 的亲和力必须在特定范围内，以使化合物从肠腔中得到令人满意的吸收。虽然这些结果应该被视为初步结果，但这项工作为分析药物相关化合物的体内吸收和分布潜力铺平了道路。这意味着对 HSA 和 IAM 的亲和力必须在特定范围内，以使化合物从肠腔中得到令人满意的吸收。虽然这些结果应该被视为初步结果，但这项工作为分析药物相关化合物的体内吸收和分布潜力铺平了道路。