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: 7220519
• 负责人: Ching Wu
• 金额: $ 9.99万
• 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 2009-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7220519
• 关键词: Acids; Alkaloids; Amino Acids; Atmospheric Pressure; Biological; Biological Markers; Biomedical Research; Buffers; Capillary Electrophoresis; Carbohydrates; Characteristics; Chemicals; Chromatography; Class; Complex Mixtures; Condition; Coupled; Data; Detection; Drug Compounding; Drug Formulations; Drug Interactions; Electrospray Ionization; Gases; Goals; High Pressure Liquid Chromatography; Hydrogen Bonding; Ions; Knowledge; Laboratories; Learning; Marketing; Mass Spectrum Analysis; Measurement; Measures; Methods; Monitor; Nucleotides; Operant Conditioning; Peptides; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physiological; Pliability; Process; Proteins; Range; Research; Research Personnel; Resolution; Sales; Sampling; Spectrometry; Speed; Staging; Structure; Supercritical Fluid Chromatography; System; Techniques; Technology; Temperature; Testing; Time; Universities; Variant; Washington; base; chiral molecule; concept; design; detector; drug development; drug discovery; enantiomer; instrument; ion mobility; mass spectrometer; method development; millisecond; novel; programs; research study; size; success

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.

描述（由申请人提供）：蛋白质组装、药物相互作用和底物识别是依赖于分子手性方向的一些重要的生理相互作用。初步结果清楚地表明，通过用手性分子修饰漂移气体，离子迁移谱可以为手性化合物提供一种新颖且快速的分离技术。与手性色谱法和毛细管电泳类似，手性离子迁移谱检测对映体混合物的能力基于分析物与中性手性修饰剂的相互作用。本研究的最终目标是开发并商业化快速手性分离和表征仪器：电喷雾电离-手性离子淌度谱仪-质谱仪（ESI-CIMS-MS）。该系统不仅可以在几毫秒内分离手性分子，而且可以将方法开发时间缩短至几分钟。 ESI-CIMS-MS 出色的分离速度和简单的方法开发使其成为许多应用的首选方法，分析时间是一个关键的考虑因素。该系统可用于直接测量药品中手性成分的对映体过量，当筛选数百种药物化合物作为候选药物时，可提高药物发现中手性测量的通量，可用于监测制备型手性分离过程的性能，或可用作色谱系统的手性选择性检测器。第一阶段研究的重点是使用所提出的系统表征生物活性手性化合物。将测试多种挥发性手性分子作为 CIMS 的手性修饰剂。该研究旨在探索可实现最大手性分离的最佳仪器条件，证明使用有效的手性修饰剂分离不同类别的生物活性手性化合物，探索利用手性修饰剂和对映体离子之间的多种气相相互作用力提高手性分辨率的可能性，分析和比较CIMS和色谱系统的手性分离特性，并探索利用手性修饰剂和对映体离子之间的多种气相相互作用力提高手性分辨率的可能性。 定量测定对映体过量的潜力。作为长期目标，还将研究使用已知手性修饰剂确定分析物手性的可能性。在第一阶段研究中学到的 CIMS 基础知识将用于在第二阶段设计和制造 ESI-CIMS-MS 系统，该系统将被商业化以支持广泛的生物医学研究。 所提出的手性离子淌度谱仪-质谱仪，可以在几秒钟内分离和识别手性化合物，有可能取代手性色谱法，因为手性分析时间是一个关键的考虑因素。快速对映体过量测量对于药物发现过程和药品 QA/QC 至关重要，因为制成药物制剂的单一对映体化合物的全球销售额达到每年 1500 亿美元。该系统还可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、代谢物和其他生物活性化合物。