Chiral Ion Mobility Spectrometry for Rapid Separation of Enantiomeric Compounds

用于快速分离对映体化合物的手性离子淌度光谱法

• 批准号: 8101833
• 负责人: Ching Wu
• 金额: $ 35.9万
• 依托单位: EXCELLIMS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8101833
• 关键词: Address; Adopted; Basic Science; Behavior; Benchmarking; Biological Markers; Biomedical Research; Buffers; Calibration; Capillary Electrophoresis; Charge; Chromatography; Complex Mixtures; Computer software; Coupled; Data; Detection; Development; Drug Compounding; Drug Formulations; Drug Industry; Drug Interactions; Electrospray Ionization; Evaluation; Gases; Goals; Health; High Pressure Liquid Chromatography; Intention; Ions; Mass Spectrum Analysis; Measurement; Measures; Methods; Molecular Structure; Monitor; Performance; Pharmacologic Substance; Phase; Physiological; Preparation; Process; Proteins; Reaction; Research; Sales; Sampling; Series; Software Design; Spectrometry; Speed; System; Techniques; Technology; Time; Tube; Variant; base; chiral molecule; cost; design; detector; drug candidate; drug discovery; enantiomer; improved; instrument; ion mobility; mass spectrometer; method development; millisecond; novel; phase 1 study; programs; research and development; success; tool

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. Key words: chiral Ion mobility spectrometer, electrospray ionization, enantiomers, pharmaceuticls, rapid chiral separation PUBLIC HEALTH RELEVANCE: 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.

描述（由申请人提供）：蛋白质的组装，药物相互作用和底物识别是取决于分子手性方向的一些重要生理相互作用。初步结果清楚地表明，通过用手性分子修饰漂移气体，离子迁移率光谱法可以为手性化合物提供新颖而快速的分离技术。与手性色谱和毛细血管电泳相似，手性离子迁移率光谱法检查对映体混合物的能力是基于分析物与中性手性修饰剂的相互作用。提出的研究的最终目标是开发和商业化快速的手性分离和表征仪器：电喷雾电离 - 手性离子迁移率光谱仪 - 质谱仪（ESI -CIMS -MS）。所提出的系统不仅可以在毫秒内分离手性分子，而且还可以将方法开发时间缩短为几分钟。 ESI-CIMS-MS的巨大分离速度和简单的方法开发使其成为许多应用分析时间的选择方法。该提出的系统可用于直接测量药品中手性成分过量的过量，可以在药物发现中增加手性测量的吞吐量，以作为药物候选药物筛选，可用于监测制备性手性分离过程的性能，或者可以用作chiral Pelective Systems的制备性手性分离过程。关键词：手性离子迁移率光谱仪，电喷雾电离，对映异构体，药物，快速手性分离 公共卫生相关性：拟议的手性离子迁移率光谱仪 - 质谱仪，分离和识别秒的手性化合物，可以潜在地替换手性色谱法以进行手性分析时间是一个关键考虑。随着全世界在药品发现过程中，快速对映体的过度测量在药物发现过程和QA/QC中至关重要，因为全世界在药品配方中生产的单一抗异构体化合物的销售额达到1500亿美元/年。所提出的系统还可以用于分析复杂混合物中的手性化合物，以定量和检测生物医学研究中的生物标志物，代谢产物和其他生物活性化合物。