Characterization of matrix effects in developing rugged high-throughput LC–MS/MS methods for bioanalysis

ABSTRACT Aim: There is an ever-increasing demand for high-throughput LC–MS/MS bioanalytical assays to support drug discovery and development. Results: Matrix effects of sofosbuvir (protonated) and paclitaxel (sodiated) were thoroughly evaluated using high-throughput chromatography (defined as having a run time ≤1 min) under 14 elution conditions with extracts from protein precipitation, liquid–liquid extraction and solid-phase extraction. A slight separation, in terms of retention time, between underlying matrix components and sofosbuvir/paclitaxel can greatly alleviate matrix effects. Conclusion: High-throughput chromatography, with proper optimization, can provide rapid and effective chromatographic separation under 1 min to alleviate matrix effects and enhance assay ruggedness for regulated...