Liquid Chromatography System with Mass-Based Analysis and Purification to Support Departmental Reaction Optimization and Medicinal Chemistry Programs

具有基于质量的分析和纯化功能的液相色谱系统，支持部门反应优化和药物化学项目

• 批准号: RTI-2020-00115
• 负责人: Hall, Dennis
• 金额: $ 10.93万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=693780
• 关键词: Liquid; Chromatography; System; Mass; Based

With discoveries like drugs, insecticides, polymers, and food additives, organic chemistry is a powerful science that has helped our modern society enjoy a dramatic increase in life expectancy and standard of living in the past century. The discovery of new drugs and commodity chemicals rely on a continuous input of new reactions and new compounds to be tested for the desired applications. In the field of drug discovery, numerous compounds must be designed, synthesized, purified and tested iteratively until an optimal molecules is identified that possesses all of the desired beneficial properties. Research laboratories of both co-applicants are actively involved in a number of focused drug discovery projects with collaborators in the Faculty of Medicine, as well as other early-stage projects aimed at developing new chemotypes and new methods to produce small molecules of medicinal interest. The technology of high-performance liquid chromatography coupled with mass spectrometric detection (LCMS) with mass-based purification is essential in various stages of these projects, for example to purify small amounts of compounds for biological testing, to perform pre- or post-assay quality control, or even to assess the stability of lead compounds under different media and storage conditions. Our current departmental LCMS instrument is a workhorse system, purchased in 2004, that is often utilized day and night (with programmed injections) for an average of 30 hours/week. This system is several generations behind current models, and is no longer supported by the vendor. It is deteriorating rapidly, which jeopardizes the progress of numerous drug discovery projects and other activities that rely on this invaluable technology. Thus, this RTI application describes a proposal to acquire a modern HPLC-ESMS system equipped with mass-based analysis and semi-preparative purification to support the daily organic synthesis activities of the co-applicants' laboratories and their numerous medicinal chemistry collaborations, particularly in oncology research. The system will be a key component of a compound purification and analysis service facility within a departmental Analytical and Instrumentation Laboratory, which also supports other programs in the U of A Department of Chemistry. It will support applied medicinal chemistry projects and other synthetic methodology development projects in all aspects of reaction optimization, analysis, and purification. The urgent need for the requested instrument is acutely illustrated by the very recent failure of the autosampler on the current obsolete instrument, which was deemed unserviceable by the original vendor. A new instrument would immediately support and enhance the training environment of over 25 HQP in the research groups of the co-applicants and others. Moreover, it would be managed and maintained, by a full-time, highly experience technologist within a dedicated departmental facility.

凭借药物、杀虫剂、聚合物和食品添加剂等发现，有机化学是一门强大的科学，在上个世纪帮助我们的现代社会实现了预期寿命和生活水平的大幅提高。新药和商品化学品的发现依赖于不断输入新反应和新化合物，以测试所需应用。在药物发现领域，必须反复设计、合成、纯化和测试大量化合物，直到确定出具有所有所需有益特性的最佳分子。两位共同申请人的研究实验室与医学院的合作者积极参与了许多重点药物发现项目，以及旨在开发新化学型和新方法来生产具有药用价值的小分子的其他早期项目。高效液相色谱技术与基于质量的纯化的质谱检测 (LCMS) 相结合，在这些项目的各个阶段都至关重要，例如纯化用于生物测试的少量化合物、进行分析前或分析后质量控制，甚至评估先导化合物在不同介质和储存条件下的稳定性。我们当前的部门 LCMS 仪器是一个主力系统，于 2004 年购买，经常日夜使用（通过编程注射），平均每周使用 30 小时。该系统比当前型号落后几代，并且供应商不再支持。它正在迅速恶化，这危及了许多依赖这种宝贵技术的药物发现项目和其他活动的进展。因此，该 RTI 申请描述了一项购买配备基于质量的分析和半制备纯化的现代 HPLC-ESMS 系统的提案，以支持共同申请人实验室及其众多药物化学合作的日常有机合成活动，特别是在肿瘤学研究。该系统将成为系内分析和仪器实验室内化合物纯化和分析服务设施的关键组成部分，该实验室还支持阿尔伯塔大学化学系的其他项目。它将支持反应优化、分析和纯化各个方面的应用药物化学项目和其他合成方法开发项目。当前过时仪器上的自动进样器最近发生故障，原供应商认为该仪器无法使用，这充分说明了对所请求仪器的迫切需要。新工具将立即支持和增强共同申请人和其他人的研究小组中超过 25 个总部的培训环境。此外，它将由专门的部门设施内的全职、经验丰富的技术专家进行管理和维护。