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

Aim: 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. Results: 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. Conclusion: The systematic method optimization strategy, and the general applicability of the optimized conditions could facilitate the routine utilization of μFLC in quantitative discovery bioanalysis.