title: A bioanalytical strategy utilizing dried blood spot sampling and LC-MS/MS in discovery toxicology studies.
abstract: METHODS
  The small sample volumes characteristic to dried blood spot (DBS) sampling enabled us to right-shift the linear dynamic range of an LC-MS/MS plasma assay tenfold and eliminate the need for extensive sample dilution in support of three discovery toxicology studies in which both plasma and DBS samples were collected. With the right-shifted DBS assay range, no DBS study samples required dilution, while all of the plasma samples were diluted 5-50-fold.
  
  
  RESULTS
  DBS standard curves from 78-80,000 nM were linear, the performance of the curve and QC samples was within acceptable discovery-assay criteria and individual plasma and DBS data were comparable. Linear correlations of C(max) and AUC derived from DBS and plasma data resulted in R(2) > 0.9.
  
  
  CONCLUSIONS
  This bioanalytical strategy represents a benefit to the bioanalyst that can expedite the return of data and minimize the potential for error and variability that can result from extensive dilutions of study samples.
authors.affiliation: Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Lorell
authors.initials: L
authors.lastname: Discenza
authors.forename: Mary T
authors.initials: MT
authors.lastname: Obermeier
authors.forename: Richard
authors.initials: R
authors.lastname: Westhouse
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Olah
authors.forename: Celia J
authors.initials: CJ
authors.lastname: D'Arienzo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000592:standards*; D004285:Dogs; D059788:Dried Blood Spot Testing / Q000592:standards*; D064420:Drug-Related Side Effects and Adverse Reactions; D008252:Macaca fascicularis; D013058:Mass Spectrometry / Q000592:standards*; D004364:Pharmaceutical Preparations / Q000032:analysis; D010949:Plasma / Q000737:chemistry*; D011786:Quality Control; D051381:Rats
chemical_list: D004364:Pharmaceutical Preparations