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.

中文翻译：

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色谱HILIC指数可表征两性离子的亲脂性。

反相高压液相色谱（RP-HPLC）在药物发现中广泛用于亲脂性测量。在确定亲水性化合物（如两性离子）的亲脂性时，亲水相互作用液相色谱法（HILIC）可以替代RP-HPLC。在本文中，将三种不同的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）组合在一起进行设置六个色谱系统。首先使用一种名为“块相关性”（BR）分析的计算工具对控制六个系统中保留的分子间力平衡进行反卷积。然后确定了十种模型两性电解质的亲脂性分布（log k对pH）。结果表明，可以使用ZIC®-cHILIC固定相和80％ACN / 20％缓冲液流动相成功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，还分析了第二种两性离子药物。