Recently, the development of cyclic peptide drugs has accelerated. To develop an analytical method to determine the physicochemical properties of these lipophilic drug candidates, we investigated the separation mechanism of cyclosporine congeners A, B, C, and D using HPLC with a column packed with 2-μm nonporous octadecylsilyl silica particles at high temperature. The four congeners were eluted with good repeatability in terms of retention time, peak area, and theoretical plate number. A difference of one amino acid in the eleven amino-acid sequence of the cyclosporine congeners was able to be recognized by our system within 4 min by isocratic elution, and the resolution was greater than 1.68. The calculated logP values of these congeners were well correlated with the retention factors with a correlation coefficient of 0.991. We could elucidate the separation mechanism of cyclosporine congeners on the high-temperature HPLC system. These results show that this method using HPLC on a column packed with 2-μm nonporous octadecylsilyl silica particles can be used for studying the lipophilicity of cyclosporine congeners.

中文翻译：

---

在发达的HPLC系统中环孢菌素同源物的洗脱行为反映了亲脂性。

近来，环肽药物的开发已经加速。为了开发一种确定这些亲脂性药物候选物理化性质的分析方法，我们使用了装有2-μm无孔十八烷基甲硅烷基二氧化硅颗粒的色谱柱，在高温下使用HPLC研究了环孢菌素同源物A，B，C和D的分离机理。在保留时间，峰面积和理论塔板数方面，四个同类物均具有良好的重复性。通过等度洗脱，我们的系统能够在4分钟内识别出环孢菌素同源物的11个氨基酸序列中一个氨基酸的差异，并且分离度大于1.68。这些同类物的计算logP值与保留因子高度相关，相关系数为0.991。我们可以阐明在高温HPLC系统上环孢菌素同源物的分离机理。这些结果表明，在填充有2μm无孔十八烷基甲硅烷基二氧化硅颗粒的色谱柱上使用HPLC的方法可用于研究环孢菌素同源物的亲脂性。