title: Application of DBS sampling in combination with LC-MS/MS for pharmacokinetic evaluation of a compound with species-specific blood-to-plasma partitioning.
abstract: BACKGROUND
  Dried blood spot (DBS) sampling in combination with LC-MS/MS has been used increasingly in drug discovery for quantitative analysis to support pharmacokinetic (PK) studies. In this study, we assessed the effect of blood-to-plasma (B:P) partitioning on the bioanalytical performance and PK data acquired by DBS for a compound AMG-1 with species and concentration-dependent B:P ratio.
  
  
  RESULTS
  B:P partitioning did not adversely affect bioanalytical performance of DBS for AMG-1. For rat, (B:P ratio of 0.63), PK profiles from DBS and plasma methods were comparable. For dog, concentration-dependence of B:P ratio was observed both in vivo and in vitro. Additional studies demonstrated concentration-dependence of the compound's unbound fraction in plasma, which may contribute to the concentration-dependence of the B:P ratio.
  
  
  CONCLUSIONS
  DBS is a promising sampling technique for preclinical pharmacokinetic studies. For compounds with high B:P ratio, caution needs to be applied for data comparison and interpretation between matrices.
authors.affiliation: Department of Pharmacokinetics & Drug Metabolism, Amgen, South San Francisco, CA 94080, USA. guifenx@amgen.com
authors.forename: Guifen
authors.initials: G
authors.lastname: Xu
authors.forename: Jiyun S
authors.initials: JS
authors.lastname: Chen
authors.forename: Ruta
authors.initials: R
authors.lastname: Phadnis
authors.forename: Tom
authors.initials: T
authors.lastname: Huang
authors.forename: Craig
authors.initials: C
authors.lastname: Uyeda
authors.forename: Marcus
authors.initials: M
authors.lastname: Soto
authors.forename: Brian
authors.initials: B
authors.lastname: Stouch
authors.forename: Mary C
authors.initials: MC
authors.lastname: Wells
authors.forename: Christopher A
authors.initials: CA
authors.lastname: James
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Carlson
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000737:chemistry; D001800:Blood Specimen Collection; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D059788:Dried Blood Spot Testing / Q000379:methods*; D007275:Injections, Intravenous; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood*; D010599:Pharmacokinetics; D010949:Plasma / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013045:Species Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D001798:Blood Proteins; D004364:Pharmaceutical Preparations