In vitro degradation of ziprasidone in human whole blood

Drug Test Anal. 2023 Feb;15(2):220-234. doi: 10.1002/dta.3393. Epub 2022 Nov 7.


A systematic study was performed into the degradation of ziprasidone in simulated postmortem blood. Fifteen potential degradation products not previously reported in the literature were observed. Four resulted from degradation in human blood, whereas the remaining products resulted from reaction with solvents: four from alkaline degradation, four from reaction with acetaldehyde, and three from reaction with acetone. To identify possible degradation products, a liquid chromatograph-diode array detector (LC-DAD) and liquid chromatograph quadrupole-time-of-flight mass spectrometer (LC-QTOF-MS) operating in auto-MS/MS mode were used. It was indicated from red-shifted UV-Vis spectra, accurate mass data, mass fragmentation data, and a deuteration experiment that the site of ziprasidone degradation, in the in vitro blood experiments, was the methylene carbon of the oxindole moiety. The major in vitro blood degradation products were proposed to be E/Z isomers of 3-ethylidene-ziprasidone. Further, another in vitro degradation product in microbially inoculated blood specimens was proposed to be 3-ethyl-ziprasidone. 3-Ethylidene-ziprasidone was hypothesized to form from the reaction of ziprasidone with acetaldehyde derived from the ethanol used to spike ziprasidone into the in vitro blood experiments. Data from two postmortem investigations were available for retrospective reanalysis. Attempts were made to detect degradation products of ziprasidone, but none were found.

Keywords: LC-QTOF-MS; degradation; postmortem toxicology; stability; ziprasidone.

MeSH terms

  • Chromatography, High Pressure Liquid / methods
  • Chromatography, Liquid / methods
  • Humans
  • Piperazines*
  • Retrospective Studies
  • Tandem Mass Spectrometry* / methods


  • ziprasidone
  • Piperazines