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Published on: February 27, 2020
Utilization of DBS within drug discovery: a simple 2D-LC-MS/MS system to minimize blood- and paper-based matrix
Graeme T Clark1, Julian J Haynes
1Department of Pharmacokinetics, Dynamics & Metabolism, Pfizer Worldwide Research & Development, Sandwich, Kent, CT13 9NJ, UK. graeme.clark@pfizer.com
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.
