Utilization of DBS Within Drug Discovery: A Simple 2D-LC–MS/MS System to Minimize Blood- and Paper-Based Matrix Effects from FTA Elute™ DBS

Abstract

Dried blood spot-based bioanalysis potentially introduces novel matrix effects that need to be eliminated or controlled. Within nonregulatory drug discovery these can be defined as ≤20% and ≤30% for nominal peak area, respectively. Controlling matrix effects for a panel of compounds by simple 1D-HPLC-MS/MS was not achievable and the optimization of 2D-HPLC-MS/MS is reported here. Simple inclusion of a 'trapping' stage was not sufficient to improve matrix effects and optimization of the reconstitution solvent, reconstitution volume and injection volume was required for a generic system to be developed. A generic 2D-LC-MS/MS system has been developed that eliminates paper-based matrix effects and eliminates or controls dried blood spot matrix effects for a panel of compounds extracted from FTA Elute™ with methanol.