title: The effect of hematocrit on assay bias when using DBS samples for the quantitative bioanalysis of drugs.
abstract: BACKGROUND
  As hematocrit levels are known to vary between individuals and with disease state, its effect on the physical characteristics of dried blood spot (DBS) samples and on the accurate quantification of analytes within these samples is examined.
  
  
  RESULTS
  The area of DBS samples decreases with increasing hematocrit levels in a linear manner on the three cellulose paper substrates tested. Furthermore, a bias was observed in the concentrations of two analytes determined in DBS samples at different hematocrits, which in some cases exceeded acceptable values, particularly for hematocrits outside normal values.
  
  
  CONCLUSIONS
  If it is expected that the hematocrit of study samples will vary from values considered normal, then its effect on the quantitative determination of an analyte in DBS samples should be investigated as part of the method development and validation. If an unacceptable effect is observed, then this will need to be addressed, by modification of the analytical method, or the inclusion of quality control samples at different hematocrit levels to show control of the assay.
authors.affiliation: Platform Technology & Science, Drug Metabolism and Pharmacokinetics, GlaxoSmithKline Research & Development, Ware, Hertfordshire, SG12 0DP, UK. philip_denniff-1@gsk.com
authors.forename: Philip
authors.initials: P
authors.lastname: Denniff
authors.forename: Neil
authors.initials: N
authors.lastname: Spooner
mesh_terms: D000082:Acetaminophen / Q000097:blood; D000634:Aminoquinolines / Q000097:blood; D016477:Artifacts; D015982:Bias; D001774:Blood Chemical Analysis / Q000379:methods*; D001800:Blood Specimen Collection / Q000379:methods* / Q000592:standards; D002482:Cellulose; D003890:Desiccation; D005260:Female; D006400:Hematocrit; D006801:Humans; D008297:Male; D010209:Paper; D004364:Pharmaceutical Preparations / Q000097:blood*; D011786:Quality Control
chemical_list: D000634:Aminoquinolines; D004364:Pharmaceutical Preparations; D000082:Acetaminophen; D002482:Cellulose; C080436:8-aminoquinoline