title: 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: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pharmacokinetics, Dynamics & Metabolism, Pfizer Worldwide Research & Development, Sandwich, Kent, CT13 9NJ, UK. graeme.clark@pfizer.com
authors.forename: Graeme T
authors.initials: GT
authors.lastname: Clark
authors.forename: Julian J
authors.initials: JJ
authors.lastname: Haynes
mesh_terms: D000818:Animals; D016477:Artifacts; D001769:Blood; D001800:Blood Specimen Collection / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D055808:Drug Discovery; D006146:Guanidines / Q000737:chemistry; D007267:Injections; D017879:Isothiocyanates / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D010209:Paper; D051381:Rats; D012997:Solvents / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
chemical_list: D006146:Guanidines; D017879:Isothiocyanates; D012997:Solvents; C054435:guanidine isothiocyanate; D000432:Methanol