Graeme T Clark1, Julian J Haynes. 1. Department of Pharmacokinetics, Dynamics & Metabolism, Pfizer Worldwide Research & Development, Sandwich, Kent, CT13 9NJ, UK. graeme.clark@pfizer.com
Abstract
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.
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.
Authors: Helena Beatriz Ferreira; Inês M S Guerra; Tânia Melo; Hugo Rocha; Ana S P Moreira; Artur Paiva; M Rosário Domingues Journal: Anal Bioanal Chem Date: 2022-07-15 Impact factor: 4.478