A bioanalytical strategy utilizing dried blood spot sampling and LC-MS/MS in discovery toxicology studies

Bioanalysis. 2012 May;4(9):1057-64. doi: 10.4155/bio.12.69.

Abstract

Background & method: 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.

Conclusion: 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.

MeSH terms

  • Administration, Oral
  • Animals
  • Area Under Curve
  • Chromatography, High Pressure Liquid / standards*
  • Dogs
  • Dried Blood Spot Testing / standards*
  • Drug-Related Side Effects and Adverse Reactions*
  • Macaca fascicularis
  • Mass Spectrometry / standards*
  • Pharmaceutical Preparations / analysis
  • Plasma / chemistry*
  • Quality Control
  • Rats

Substances

  • Pharmaceutical Preparations