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

Background: 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. Results: 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. Conclusion: 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.