Superficially Porous Silica Based Chiral Stationary Phases for High Efficiency and High Speed Pharmaceutical Analysis and Purification

 描述(申请人提供)：对映体的分离(即手性分离)在开发安全的手性药物和研究其他具有光学活性的生物相关分子方面非常重要。对于手性的药物化合物，通常一个对映体(右旋或左旋)是药物，而另一半会引起副作用，不同的效果，相似的效果，或在有限的情况下，没有效果。这一SBIR项目将支持基于表面多孔颗粒(SPP)的手性固定相(CSPs)的开发。SPPS是硅胶基色谱载体，具有坚固、不透水的核心，与传统的全多孔颗粒(FFP)相比，可以极大地改进柱填充材料。我们的初步结果首次证明了刷型手性选择器与SPP键合的可行性。结果表明，与类似的基于FPP的CSP相比，SPP的多孔部分可以获得相似的手性选择器表面覆盖率，从而产生相同的对映体选择性值。与使用类似手性选择剂的商业色谱柱相比，基于SPP的CSPs的柱效率大大提高，而分析时间缩短了50%-75%。当调整流动相条件使其在商业FPP色谱柱和新的SPP手性色谱柱上保留时间相近时，分离度几乎翻了一番。此外，SPP填充柱可以在高流速下使用，而不会损失通常与本领域手性柱的当前状态相关的分离性能。正因为如此，我们已经展示了基于SPP的CSPs用于在秒的时间尺度上执行超快手性分离。这一第二阶段SBIR方案的目的是开发一些独特的手性选择剂用于商业化，这些选择剂将提供一系列稳定的、键合的、刷型的基于SPP的CSP，这些CSP可以用于任何模式的LC/SFC，并可以提供广泛的选择性/高的对映体分离成功率，大大减少分析时间。具体地说，我们将开发这些CSP的生产手段(即合成和包装方法)，测试它们的重现性，建造原型柱供我们目标市场的专家进行评估，完善扩大程序以准备生产，并开始营销并与合作伙伴、分销商和未来的投资者建立战略联盟。作为这项拟议工作的结果，这项技术将为市场带来一种新的工具，它将允许生产更好、更便宜、副作用更少、剂量更低的药品。这些CSP将在药物、医药和合成有机化学中作为分离介质发挥重要作用。

 DESCRIPTION (provided by applicant): The separation of enantiomers (i.e., chiral separations) is of great importance in the development of safe chiral pharmaceuticals and the study of other optically active biologically relevant molecules. For pharmaceutical compounds that are chiral, usually one enantiomer (either the right or left-handed version) is the drug, whil the other half causes side effects, different effects, similar effects or in limited cases, no effets. This SBIR project will support the development of superficially porous particle (SPP) based chiral stationary phases (CSPs). SPPs are silica based chromatographic supports that possess a solid, impermeable core which can result in greatly improved column packing materials compared to traditional fully porous particles (FPPs). Our preliminary results demonstrated feasibility (for the first time) of bonding brush-type chiral selectors to SPPs. It was determined that similar chiral selector surface coverage of the porous portion of the SPPs could be obtained when compared to analogous FPP based CSPs, resulting in equivalent enantiomeric selectivity values. Column efficiencies of the SPP based CSPs were greatly improved compared to commercial columns with analogous chiral selectors, while the analysis times were 50-75% shorter. When mobile phase conditions were adjusted to give similar retention times on a commercial FPP column and a new SPP chiral column, resolution values nearly doubled. Further, SPP packed columns can be used at high flow rates without the loss in separation performance typically associated with the current state of the art chiral columns. Because of this, we have demonstrated the use of SPP based CSPs for ultra-fast chiral separations being performed in the seconds' time-scale. The aim of this Phase II SBIR proposal is to develop a number of unique chiral selectors for commercialization which will offer an array of stable, bonded, brush-type SPP based CSPs that can be used in any mode of LC/SFC and can offer broad selectivity/high success rates for enantiomeric separations with greatly reduced analysis times. Specifically, we will develop the production means for these CSPs (i.e., synthesis and packing methods), test their reproducibility, build prototype columns for evaluation by experts in our target market, refine scale-up procedures to prepare for manufacturing, and begin marketing and forming strategic alliances with partners, distributors, and future investors. As a result of tis proposed work, this technology will bring to market a new tool that will allow for the production of better and less expensive pharmaceutical products that have fewer side effects and can be given in lower doses. These CSPs will play a major role as separation media in pharmaceutical, medicinal, and synthetic organic chemistry.