University of Torino, Molecular Biotechnology and Health Sciences Department, CASSMedChem, via Quarello 15, 10135 Torino, Italy.
University of Torino, Molecular Biotechnology and Health Sciences Department, CASSMedChem, via Quarello 15, 10135 Torino, Italy.
Eur J Pharm Sci. 2020 Mar 30;145:105232. doi: 10.1016/j.ejps.2020.105232. Epub 2020 Jan 23.
Reverse phase high pressure liquid chromatography (RP-HPLC) is widely employed in drug discovery for lipophilicity measurements. Hydrophilic interaction liquid chromatography (HILIC) may represent a good alternative to RP-HPLC in the determination of the lipophilicity of hydrophilic compounds like zwitterions. In this paper three different HILIC stationary phases (ZIC®-HILIC, ZIC®-pHILIC and ZIC®-cHILIC) and two different mobile phases (80%ACN/20%buffer and 90%ACN/10%buffer) were combined to set-up six chromatographic systems. A computational tool named Block Relevance (BR) analysis was firstly used to deconvolute the balance of intermolecular forces governing retention in the six systems. Then the lipophilicity profiles (log k vs pH) of ten model ampholytes were determined. Results support that the lipophilicity of zwitterions at any pH can be successfully determined with a ZIC®-cHILIC stationary phase and an 80%ACN/20%buffer mobile phase. To extend the dataset and confirm results, a second series of zwitterionic drugs was also analyzed.
反相高效液相色谱（RP-HPLC）广泛应用于药物发现中的亲脂性测量。亲水作用液相色谱（HILIC）在测定两性离子等亲水性化合物的亲脂性方面可能是 RP-HPLC 的良好替代品。在本文中，我们组合了三种不同的 HILIC 固定相（ZIC®-HILIC、ZIC®-pHILIC 和 ZIC®-cHILIC）和两种不同的流动相（80%ACN/20%缓冲液和 90%ACN/10%缓冲液），建立了六种色谱系统。首先使用一种名为 Block Relevance（BR）分析的计算工具来解卷积控制在这六个系统中保留的分子间力的平衡。然后，我们测定了十种模型两性离子的亲脂性轮廓（log k 与 pH 的关系）。结果表明，使用 ZIC®-cHILIC 固定相和 80%ACN/20%缓冲液流动相可以成功地测定两性离子在任何 pH 值下的亲脂性。为了扩展数据集并确认结果，我们还分析了另一组两性离子药物。
