Evaluation of matrix microsampling methods for therapeutic drug candidate quantification in discovery-stage rodent pharmacokinetic studies

Bioanalysis. 2014 Aug;6(16):2135-46. doi: 10.4155/bio.14.184.

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.

Materials & 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%.

Conclusion: 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.

MeSH terms

  • Animals
  • Benzothiazoles / blood*
  • Benzothiazoles / pharmacokinetics
  • Blood Specimen Collection / methods
  • Chromatography, High Pressure Liquid / methods*
  • Drug Discovery
  • Male
  • Mice
  • Pharmacokinetics
  • Pyrimidines / blood*
  • Pyrimidines / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry / methods*
  • Triazoles / blood*
  • Triazoles / pharmacokinetics

Substances

  • Benzothiazoles
  • N-(4-(6-(4-trifluoromethylphenyl)pyrimidin-4-yloxy)benzothiazol-2-yl)acetamide
  • Pyrimidines
  • Triazoles
  • 1-aminobenzotriazole