New HILIC Materials for Separating Polar Drugs, Biologics, and Metabolites

描述（由申请人提供）：药物化合物及其代谢物的有效分离和分析对于开发新的，更有效，更安全，更经济的药物的研究人员至关重要。新型生物衍生药物化合物（生物制剂）正变得越来越重要和流行，因为它们与传统的小合成分子相匹配，有时甚至超过了它们的重要性。然而，长期建立的高效液相色谱（HPLC）技术往往不能提供有效分离这些生物制剂的手段，这些生物制剂通常是高极性分子。近年来，亲水相互作用液相色谱（HILIC）已成为分析高极性药物的首选分析技术。HILIC可能是发展最快的HPLC技术，但市售的固定相可能并不总是能够执行所有期望/需要的分离。第一阶段小企业创新研究（SBIR）项目的目的是展示使用/开发一种基于天然环果聚糖的新型HILIC HPLC固定相的可行性。因此，环果聚糖的HILIC相可能是理想的，以满足日益增长的分离高极性生物相关性化合物的需要。初步结果表明，环果聚糖在其天然形式可以进行临界分离，现有的HILIC相不能。设想环果聚糖的独特结构特征（冠醚核心与悬垂的果糖呋喃糖单元）将提供一种与商业HILIC色谱柱相比可以执行独特分离的HILIC分离剂。此外，明智的流动相选择可以允许环果聚糖HILIC柱以不同的方式使用，通过环果聚糖的亲水性糖部分分离中性极性，通过与环果聚糖的冠醚的离子相互作用分离阳离子，以及通过在流动相中使用高浓度的阳离子来创建可经历独特阴离子相互作用的阳离子吸附固定相来分离阴离子。该研究的第二阶段将通过扩大色谱柱的生产能力、评估色谱柱和批量重现性以及使用原型色谱柱进行beta测试来开发该技术。最终，这项创新技术将被推向市场，并将为研究人员提供提高高极性生物相关化合物的保留率和选择性的能力，这是开发新药所必需的。

DESCRIPTION (provided by applicant): The effective separation and analysis of pharmaceutical compounds and their metabolites is essential to researchers that develop new, more effective, safer, and economical medicines. Novel types of biologically derived drug compounds (biologics) are becoming more important and prevalent as they match and sometimes exceed the importance of traditional small synthetic molecules. However, long-established high performance liquid chromatographic (HPLC) techniques often do not provide a means to effectively separate these biologics, which are typically highly polar molecules. Recently, hydrophilic interaction liquid chromatography (HILIC) has emerged as the analytical technique of choice to analyze highly polar drugs. HILIC is perhaps the fastest growing HPLC technique, but the commercially available stationary phases may not always be able to perform all the desired/needed separations. The aim of this Phase I Small Business Innovation Research (SBIR) project is to show feasibility in using/developing a new HILIC HPLC stationary phase based on native cyclofructan. It is proposed that the cyclofructan HILIC phase may be ideal in meeting the increasing need to separate highly polar compounds of biological relevance. Initial results indicate cyclofructan in its native form may perform critical separation that existing HILIC phases cannot. It is envisioned that the unique structural features of cyclofructan (crown ether core with pendent fructofuranose units) will afford a HILIC separating agent that can perform unique separations compared to commercial HILIC columns. Further, judicious mobile phase selection may allow for the cyclofructan HILIC column to be used in different ways to separate neutral polars through cyclofructan's hydrophilic sugar moieties, cations though ion interactions with cyclofructan's crown ether, and anions by using high concentrations of cations in the mobile phase to create a cation adsorbed stationary phase that can undergo unique anion interactions. Phase II of this research will then be used to develop this technology by scaling-up column production capabilities, evaluating column and batch reproducibility, and performing beta testing with prototype columns. Ultimately, this innovative technology will be brought to market and will offer researchers the ability to achieve improved retention and selectivity of highly polar biologically relevant compounds, which is a necessity in the development of new pharmaceuticals.