High-Throughput\nAssessment of Bile Salt Export Pump\nInhibition Using RapidFire-MS and DESI-MS

The\nbile salt export pump (BSEP) assay is widely used to evaluate\nthe potential for drug-induced liver injury (DILI) early in the drug\ndiscovery process. While traditional liquid chromatography–mass\nspectrometry (LC-MS)-based approaches have been utilized for BSEP\nactivity testing, they have intrinsic limitations in either throughput\nor the requirement for sample preparation and are difficult to scale\nup in order to screen drug candidates. Here we demonstrate the use\nof two different high-throughput MS methods based on solid-phase extraction\n(SPE) and desorption electrospray ionization (DESI) for high-throughput\nBSEP activity assessment in a label-free manner, with minimal needs\nfor sample workup, at sampling rates of ∼11 and ∼5.5\ns/sample, respectively. Both approaches were validated, compared,\nand successfully applied to the evaluation of 96 drug candidates for\nthe inhibition of taurocholic acid (TCA) transport using BSEP vesicles.