Drug monitoring by volumetric absorptive microsampling: method development considerations to mitigate hematocrit effects

Bioanalysis. 2018 Feb;10(4):241-255. doi: 10.4155/bio-2017-0221. Epub 2018 Jan 15.

Abstract

Aim: GSKA is a compound that was in development in clinical trials. A bioanalysis method to quantify GSKA using volumetric absorptive microsampling (VAMS) was developed and hematocrit (HCT) related assay bias was investigated.

Methodology: After accurate sampling of 10 μl blood, VAMS tips were air dried approximately 18 h and desorbed by an aqueous solution containing internal standard. The recovered blood underwent liquid-liquid extraction in ethyl acetate to minimize matrix suppression. Assay accuracy, precision, linearity, carryover, selectivity, recovery, matrix effects, HCT effects and long-term quality control stability were evaluated.

Conclusion: HCT-related assay bias was minimized in 30-60% blood HCT range, and all validation parameters met acceptance criteria. The method is suitable for quantitative analysis of GSKA in human blood.

Keywords: LC–MS/MS; dried blood spot (DBS); hematocrit (HCT); matrix effect; microsampling; pharmacokinetics (PK); regulated bioanalysis; toxicokinetics (TK); volumetric absorptive microsampling (VAMS) device.

Publication types

  • Evaluation Study

MeSH terms

  • Calibration
  • Chromatography, Liquid
  • Drug Monitoring / methods*
  • Hematocrit / methods*
  • Humans
  • Pharmaceutical Preparations / blood*
  • Reference Standards
  • Tandem Mass Spectrometry

Substances

  • Pharmaceutical Preparations