反相/亲水/阳离子交换混合模式色谱固定相的制备及在药物分离中的应用

Preparation of a Reversed-phase/Hydrophilic Interaction/Cation Exchange Mixed-mode Stationary Phase and Its Application in Drug Separation

通过巯基-烯点击化学方法,合成了一种新型双配体苯磺酸混合模式固定相(Ph/BS),通过元素分析和13C固体核磁共振进行表征。根据溶质结构和流动相组成不同,该混合模式固定相可提供反相(RP)、亲水(HILIC)和强阳离子交换(SCX)多种作用模式。反相条件下分离苯同系物,体现了较好的亚甲基选择性。使用小分子核苷和碱基对亲水色谱行为进行了评价;溶质的保留因子随流动相中水相含量的变化呈现典型的U型曲线,说明Ph/BS固定相具有RP/HILIC双重保留机理。胺类化合物在该固定相上的保留体现了RP/SCX混合色谱的特征。另外,应用Ph/BS固定相在SCX模式下高效分离了二甲双胍及其杂质,在RP/SCX模式下同时分离了酸性、中性和碱性药物。结果显示,该混合模式固定相在复杂样品的分离分析方面具有潜在的优势。

A novel benzenesulfonate silica-based mixed-mode stationary phase with double-ligand was prepared by thiol-ene click chemistry method.Both 13 C NMR and elemental analysis data showed that the phenyl and benzenesulfonate were successfully bonded to the surface of stationary phase.Depending on solute structure and composition of mobile phase,the mixed mode stationary phase provided different separation modes,including reversed-phase(RP),hydrophilic(HILIC)and strong cation exchange(SCX)interactions.The RP capability achieved the separation of alkylbenzenes with good methylene selectivity.The HILIC behavior was evaluated by employing several nucleosides and bases.Moreover,retention factors of solutes versus volume percentage of aqua in mobile phase exhibited a typical U-shaped curve,which indicated that Ph/BS phase has RP and HILIC dual retention mechanism.The retention behavior of amine compounds on the stationary phase reflected RP and SCX mixed mode retention characteristic.In addition,the effective separation of melamine and related purities was obtained in SCX mode.Acidic,neutral and basic drugs were also well separated under the RP and SCX mixed mode conditions.This mixed mode stationary phase has the potential advantages in the separation analysis of complex samples.