Development and Validation of HILIC-ESI/MS/MS Methods for Simultaneous Quantitation of Several Antipsychotics in Human Plasma and Blood

Bioanalysis. 2016 Apr;8(8):765-94. doi: 10.4155/bio.16.27. Epub 2016 Mar 23.

Abstract

Background: Knowledge of antipsychotic drug levels at point of care (POC) may significantly aid therapeutic decision-making. To support the development of future POC devices and to validate the use of fingerstick capillary blood sampling, two robust hydrophilic interaction LC-ESI/MS/MS methods were developed and validated. Two PK studies were completed evaluating the correlation between fingerstick blood and plasma concentrations with corresponding venous blood and plasma concentrations for several commonly prescribed atypical antipsychotics and selected metabolites. Sensitive and reliable LC-MS/MS bioanalytical assays were developed to support these studies.

Results: Three methods, requiring only 25-μl matrix volumes, were developed using supported liquid extraction with hydrophilic interaction LC-MS/MS detection and validated according to regulatory guidance.

Conclusion: Robust and efficient LC-MS/MS assays were established and were effective in providing antipsychotic drug matrix comparator results in the intended clinical studies.

Keywords: HILIC; LC–MS/MS; SLE; antipsychotics; fingerstick blood sampling; method validation.

Publication types

  • Validation Study

MeSH terms

  • Antipsychotic Agents / blood*
  • Antipsychotic Agents / pharmacokinetics
  • Antipsychotic Agents / standards
  • Blood Chemical Analysis / methods*
  • Blood Chemical Analysis / standards
  • Calibration
  • Chromatography, High Pressure Liquid* / standards
  • Half-Life
  • Humans
  • Point-of-Care Systems
  • Reproducibility of Results
  • Spectrometry, Mass, Electrospray Ionization* / standards

Substances

  • Antipsychotic Agents