title: Evaluation of matrix microsampling methods for therapeutic drug candidate quantification in discovery-stage rodent pharmacokinetic studies.
abstract: BACKGROUND
  AMG 517 or 1-aminobenzotriazole were quantified by LC-MS/MS from low blood/plasma volumes for rat pharmacokinetic (PK) characterization in order to qualify manual/automated dried blood spot (DBS) sampling and plasma separation capillary sampling. In addition, mouse serial automated blood sampling was compared with standard composite sampling.
  
  
  METHODS
  AMG 517 or 1-aminobenzotriazole was administered to rats or mice and multiple microsampling techniques were used to obtain blood or plasma.
  
  
  RESULTS
  PK parameters derived from DBS and whole blood-obtained drug concentrations were within 7% for manual DBS and 20% for automated DBS. Plasma PK parameters derived from capillary or standard plasma-obtained drug concentrations differed by 6%. Plasma PK parameters obtained from serial automated blood sampling or manual composite sampling were within 20%.
  
  
  CONCLUSIONS
  Collectively, these results suggest that the microsampling applications that were investigated are attractive approaches for quantifying drug candidates in low matrix volumes that can be successfully employed within discovery-stage rodent PK studies.
authors.affiliation: Department of Pharmacokinetics & Drug Metabolism, Amgen, Inc., Thousand Oaks, CA 91320, USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Soto
authors.forename: Roger
authors.initials: R
authors.lastname: Pham
authors.forename: Valerie
authors.initials: V
authors.lastname: Almon
authors.forename: Mylo
authors.initials: M
authors.lastname: Wagner
authors.forename: Ronya
authors.initials: R
authors.lastname: Primack
authors.forename: Manuel
authors.initials: M
authors.lastname: Ponce
authors.forename: James
authors.initials: J
authors.lastname: Meyer
authors.forename: Christopher A
authors.initials: CA
authors.lastname: James
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Salyers
authors.forename: Marc W
authors.initials: MW
authors.lastname: Retter
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000097:blood* / Q000493:pharmacokinetics; D001800:Blood Specimen Collection / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D055808:Drug Discovery; D008297:Male; D051379:Mice; D010599:Pharmacokinetics; D011743:Pyrimidines / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014230:Triazoles / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D052160:Benzothiazoles; C523409:N-(4-(6-(4-trifluoromethylphenyl)pyrimidin-4-yloxy)benzothiazol-2-yl)acetamide; D011743:Pyrimidines; D014230:Triazoles; C033020:1-aminobenzotriazole