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

Aim: The sensitivity advantage of microflow LC (mu FLC)-MS/MS is potentially impactful for challenging compounds not detectable by conventional flow LC-MS/MS in drug discovery bioanalysis. Relatively new to mu FLC technology, discovery bioanalytical scientists would benefit from an effective strategy for method development and optimization. Results: A systematic mu FLC-MS/MS method optimization approach was developed in this study. Withoptimized conditions, mu FLC-MS/MS demonstrated an improved sensitivity compared with conventional LC-MS/MS analysis, ranging from 6x to 49x (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 mu FLC in quantitative discovery bioanalysis.