?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.
Public Health Relevance Statement: Public Health Relevance: Pharmaceutical compounds that are chiral (from the Greek word for "hand") can exist as enantiomers (i.e., right and left-handed versions of the same basic compound) and for medicines of this sort, usually one enantiomer (either the right or left-handed version) is the drug, while the other half causes side effects, different effects, similar effects r in limited cases, no effects. In our proposed research we introduce a new technology for the analysis and purification of chiral drugs which utilizes specialized packing materials called superficially porous particle based chiral stationary phases, which in our feasibility studies proved to offer the ability to reduce chiral drug analysis times from tens of minutes to tens of seconds by greatly increasing the efficiency of the analysis and improving the ability to rapidly, separate and purify most classes of chiral pharmaceutical compounds, as well as, other biologically relevant chiral molecules. As a result of this proposed work, Americans will have better and less expensive pharmaceutical products that have fewer side effects and can be given in lower doses, and scientists will have better means to study stereo selective effects of chiral biological molecules.
Project Terms: Accounting; Adverse effects; American; Area; base; Biological; chiral molecule; Chromatography; Column Chromatography; commercialization; Complex; Cyclodextrins; Development; Dose; enantiomer; Ensure; Evaluation; Feasibility Studies; Funding; Future; Greek; Growth; Hand; High Pressure Liquid Chromatography; improved; innovative technologies; Left; Liquid substance; Marketing; Medicine; Methods; molecular recognition; Neck; new technology; North America; novel; Organic Chemistry; particle; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Play; Preclinical Drug Evaluation; Preparation; Procedures; Process; Production; prototype; public health relevance; Reproducibility; Research; Resolution; Role; Sales; scale up; Scientist; screening; Secure; Silicon Dioxide; Small Business Innovation Research Grant; Solid; Sorting - Cell Movement; Speed (motion); stability testing; success; Surface; Technology; Teicoplanin; Testing; Time; tool; Vancomycin; Work
