College of Life Sciences, Nankai University, Tianjin 300071, China.
Protein Cell. 2011 Aug;2(8):680-8. doi: 10.1007/s13238-011-1086-2. Epub 2011 Sep 9.
Improving analytical throughput is the focus of many quantitative workflows being developed for early drug discovery. For drug candidate screening, it is common practice to use ultra-high performance liquid chromatography (U-HPLC) coupled with triple quadrupole mass spectrometry. This approach certainly results in short analytical run time; however, in assessing the true throughput, all aspects of the workflow needs to be considered, including instrument optimization and the necessity to re-run samples when information is missed. Here we describe a high-throughput metabolic stability assay with a simplified instrument set-up which significantly improves the overall assay efficiency. In addition, as the data is acquired in a non-biased manner, high information content of both the parent compound and metabolites is gathered at the same time to facilitate the decision of which compounds to proceed through the drug discovery pipeline.
提高分析通量是许多正在开发的早期药物发现定量工作流程的重点。对于候选药物筛选,通常使用超高效液相色谱(U-HPLC)与三重四极杆质谱联用。这种方法确实可以缩短分析运行时间;但是,在评估真实的通量时,需要考虑工作流程的各个方面,包括仪器优化和在信息丢失时需要重新运行样品。在这里,我们描述了一种具有简化仪器设置的高通量代谢稳定性测定法,这显著提高了整体测定效率。此外,由于数据是以无偏的方式采集的,因此可以同时获得母体化合物和代谢物的高信息量,从而有助于决定哪些化合物进入药物发现管道。