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High Throughput Concurrent Determination of Compound Solubility and Purity Employing a Low Volume Parallel Liquid Chromatography System with MS Capability

机译:高通量同时测定具有MS能力的低体积平行液相色谱系统的化合物溶解度和纯度

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Compound purity and solubility (at the usual pH range present in the GI tract) should be determined during drug lead optimization to aid in the selection of promising drug candidates prior to biological testing to make certain that screening results will be meaningful. The evaluations of compound purity and solubility employing traditional approaches are often inadequate in modern HTS due to the throughput and sample amount limitations imposed by these approaches. Some of the techniques used for solubility evaluations, such as nephelometry and flow cytometry, provide adequate throughput but are not sensitive to compound purity and identity. Conventional HPLC and LC-MS methods overcome these drawbacks but suffer from their intrinsic low throughput nature when used in a serial mode. Micro parallel liquid chromatography coupled with mass spectrometry offers the advantages of a separation based approach (such as HPLC and LC-MS) and allows for high-throughput chemical analysis with increased sample capacity and reduced sample consumption, solvent usage, and waste generation
机译:化合物纯度和溶解性(在存在于胃肠道中的通常pH范围内)应药物先导物优化过程中确定在生物测试之前,将有希望的候选药物的选择,以帮助做出一定的筛选的结果将是有意义的。化合物纯度和溶解性的采用传统方法的评价是在现代HTS往往不足由于吞吐量和由这些方法所施加的样品量的限制。一些用于溶解性评价的技术,如比浊法和流式细胞术,提供足够的吞吐量,但是不应化合物纯度和身份敏感。传统的HPLC和LC-MS方法克服了这些缺点,但在串行模式下使用时,来自其固有的低产量自然受到影响。微平行与质谱联用优惠分离为基础的方法的优点(如HPLC和LC-MS)液相色谱法,并允许具有增加的样品容量高通量化学分析和减少的样品量,溶剂用量,和废物产生

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