Optimization of microflow LC-MS/MS and its utility in quantitative discovery bioanalysis.

The sensitivity advantage of microflow LC (μFLC)-MS/MS is potentially impactful for challenging compounds not detectable by conventional flow LC-MS/MS in drug discovery bioanalysis. Relatively new to μFLC technology, discovery bioanalytical scientists would benefit from an effective strategy for method development and optimization. A systematic μFLC-MS/MS method optimization approach was developed in this study. With optimized conditions, μFLC-MS/MS demonstrated an improved sensitivity compared with conventional LC-MS/MS analysis, ranging from 6× to 49× (by peak area) depending on the compounds, with acceptable analytical performance and robustness. The optimized conditions demonstrated universal applicability to various compounds of diverse properties. The systematic method optimization strategy, and the general applicability of the optimized conditions could facilitate the routine utilization of μFLC in quantitative discovery bioanalysis.