Simulation of phase I metabolism reactions of clozapine by HLM and photocatalytic methods with the use of UHPLC-ESI-MS/MS

Biomed Chromatogr. 2018 Oct;32(10):e4297. doi: 10.1002/bmc.4297. Epub 2018 Jun 27.

Abstract

In this study the comparison of human liver microsomes in in vitro incubation as well as ZnO- and TiO2 -assisted photocatalytic degradation of clozapine as a mimicking method of phase I metabolism transformation was performed. Based on reversed-phase UHPLC separation and high-resolution MS/MS data, eight transformation products were identified and seven of them were found to be hepatic metabolites of the parent compound. The multivariate chemometric comparison of the obtained results shows ZnO-assisted photocatalysis to be a more suitable approach to phase I metabolism simulation. The photocatalytic experiments demonstrated that the disappearance of clozapine followed pseudo-zero order kinetics.

Keywords: HLM; Q-TOF; UHPLC; metabolism; photocatalysis.

MeSH terms

  • Chromatography, High Pressure Liquid / methods*
  • Clozapine / analysis
  • Clozapine / chemistry
  • Clozapine / metabolism*
  • Humans
  • Microsomes, Liver / metabolism
  • Photolysis*
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry / methods*
  • Titanium / chemistry
  • Zinc Oxide / chemistry

Substances

  • titanium dioxide
  • Titanium
  • Clozapine
  • Zinc Oxide