高分辨精确质量方法和自动数据挖掘驱动高通量代谢物稳定性研究

前言：

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 times; 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.

A high-throughput metabolic stability assay with a simplified instrument set up significantly improves overall assay efficiency. In addition, as the data collection is nonbiased, information on the parent compound and metabolites is gathered at the same time.

Here a high-throughput metabolic stability assay with a simplified instrument set up is described that significantly improves overall assay efficiency.

仪器：

Thermo Scientific Exactive high performance benchtop LC-MS

结论：

A highly efficient quantitative/qualitative metabolic stability assay was established using HRMS that shows significant advantages over triple quadrupole-based methods with regards to overall throughput, data quality, and information content. U-HPLC coupled with the Exactive LC-MS system scanning at high resolution and followed by automated post-acquisition data processing provides specific advantages over traditional triple quadrupole-based methods including:

• Analytical time is significantly reduced with no need for MS/MS optimization.

• Information content is expanded by monitoring both the parent and various possible metabolites.

• Post-run re-interrogation of data allows users to identify and quantitate additional components as they become of interest.