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

描述(由申请人提供)：有效地分离和分析药物化合物及其代谢物对于开发新的、更有效、更安全和经济的药物的研究人员是必不可少的。新型的生物衍生药物化合物(生物制品)正变得越来越重要和普遍，因为它们与传统的合成小分子相匹配，有时甚至超过了它们的重要性。然而，建立已久的高效液相色谱(HPLC)技术往往不能提供有效分离这些生物制品的方法，这些生物制品通常是高极性分子。近年来，亲水相互作用液相色谱(HILIC)已成为分析强极性药物的首选分析技术。HILIC可能是发展最快的高效液相色谱技术，但商业上可用的固定相可能并不总是能够执行所有所需的分离。这一第一阶段小型企业创新研究(SBIR)项目的目的是证明使用/开发一种基于天然环果聚糖的新的HILIC高效液相色谱固定相的可行性。有人提出，在满足日益增长的分离具有生物相关性的高极性化合物的需求方面，环果聚糖HILIC相可能是理想的。初步结果表明，天然形式的环果聚糖可以实现现有HILIC相所不能实现的临界分离。可以预见，环果聚糖(具有悬挂的呋喃果糖单元的冠醚核心)的独特结构特征将提供一种HILIC分离剂，与商用HILIC柱相比，它可以执行独特的分离。此外，明智的流动相选择可以允许以不同的方式使用环果聚糖HILIC柱，以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离子相互作用分离阳离子，以及通过使用流动相中高浓度的阳离子来创建可进行独特阴离子相互作用的阳离子吸附固定相。然后，这项研究的第二阶段将用于开发这项技术，方法是扩大色谱柱的生产能力，评估色谱柱和批次的重现性，并用原型色谱柱进行Beta测试。最终，这项创新技术将推向市场，并将为研究人员提供提高高度极性生物相关化合物的保留率和选择性的能力，这是开发新药物所必需的。

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.