Chiral Ion Mobility Spectrometry for Rapid Separation of Enantiomeric Compounds

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DESCRIPTION (provided by applicant): Assembly of proteins, drug interactions, and substrate recognition are a few of the vital physiological interactions that depend on the chiral orientation of molecules. Preliminary results clearly demonstrate that by modifying the drift gas with chiral molecules, ion mobility spectrometry can provide a novel and rapid separation technique for chiral compounds. Similar to chiral chromatography and capillary electrophoresis, the ability of chiral ion mobility spectrometry to examine enantiomeric mixtures is based upon the interaction of analytes with neutral chiral modifiers. The ultimate goal of the research proposed is to develop and commercialize the rapid chiral separation and characterization instrument: electrospray ionization - chiral ion mobility spectrometer - mass spectrometer (ESI-CIMS-MS). The proposed system can not only separate chiral molecules in milliseconds, but also reduce method development time to minutes. Great separation speed and easy method development of ESI-CIMS-MS make it the method of choice for many applications analysis time is a critical consideration. The proposed system can be used to directly measure enantiomeric excess of chiral ingredients in pharmaceutical products, may serve to increase throughput for chirality measurements in drug discovery when hundreds of drug compounds are being screened as drug candidates, can be used to monitor the performance of preparative chiral separation processes, or can be used as a chiral selective detector for chromatographic systems. The Phase I research focuses on the characterization of bioactive chiral compounds with the proposed system. A broad range of volatile chiral molecules will be tested as chiral modifier for the CIMS. The research seeks to explore optimal instrumental conditions where maximum chiral separation can be achieve, to demonstrate the separation of different classes of biologically active chiral compounds with effective chiral modifiers, to explore the possibility of enhancing chiral resolution using multiple gas phase interaction forces between chiral modifier and enantiomeric ions, to analyze and compare chiral separation characteristics of CIMS and chromatographic systems, and to explore the potential of quantitative determination of enantiomeric excess. As a longer term goal, the possibility of determining analytes chirality of using known chiral modifier will also be examined. The fundamental knowledge of the CIMS learned in the Phase I research will be used to design and fabricate an ESI-CIMS-MS system in Phase II, which will be commercialized to support a wide range of biomedical research. Proposed chiral ion mobility spectrometer - mass spectrometer, separating and identifying chiral compounds in seconds, can potentially replace chiral chromatography for chiral analysis time is a critical consideration. Rapid enantiomeric excess measurement is essential in drug discovery process and QA/QC of pharmaceutical products as worldwide sales of single-enantiomer compounds made into the pharmaceutical formulations reaches $150 billion/year. The proposed system can also be used for the analysis of chiral compounds in complex mixture for quantification and detection of biomarkers, metabolites and other bioactive compounds in biomedical research.