Identification and quantification of the antipsychotics risperidone, aripiprazole, pipamperone and their major metabolites in plasma using ultra-high performance liquid chromatography-mass spectrometry

Biomed Chromatogr. 2016 Jun;30(6):794-801. doi: 10.1002/bmc.3610. Epub 2015 Oct 8.

Abstract

The antipsychotics risperidone, aripiprazole and pipamperone are frequently prescribed for the treatment in children with autism. The aim of this study was to validate an ultra-high performance liquid chromatography-mass spectrometry method for the quantification of these antipsychotics in plasma. An ultra-high performance liquid chromatography-mass spectrometry assay was developed for the determination of the drugs and metabolites. Gradient elution was performed on a reversed-phase column with a mobile phase consisting of ammonium acetate, formic acid in methanol or in Milli-Q ultrapure water at a flow rate of 0.5 mL/min. The method was validated according to the US Food and Drug Administration guidelines. The analytes were found to be stable enough after reconstitution and injection of only 5 μL improved the accuracy and precision in combination with the internal standard. Calibration curves of all five analytes were linear. All analytes were stable for at least 72 h in the autosampler and the high quality control of 9-OH-risperidone was stable for 48 h. The method allows quantification of all analytes. The advantage of this method is the combination of a minimal injection volume, a short run-time, an easy sample preparation method and the ability to quantify all analytes in one run. Copyright © 2015 John Wiley & Sons, Ltd.

Keywords: UPLC-MS/MS; antipsychotic drugs; pharmacokinetics; children; therapeutic drug monitoring.

Publication types

  • Validation Study

MeSH terms

  • Antipsychotic Agents / blood*
  • Aripiprazole / blood
  • Butyrophenones / blood
  • Chromatography, High Pressure Liquid / methods*
  • Humans
  • Limit of Detection
  • Reference Standards
  • Reproducibility of Results
  • Risperidone / blood
  • Tandem Mass Spectrometry / methods*

Substances

  • Antipsychotic Agents
  • Butyrophenones
  • pipamperone
  • Aripiprazole
  • Risperidone