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Simulation of phase I metabolism reactions of clozapine by HLM and photocatalytic methods with the use of UHPLC‐ESI‐MS/MS
Author(s) -
Gawlik Maciej,
Skibiński Robert
Publication year - 2018
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4297
Subject(s) - chemistry , photocatalysis , chromatography , phase (matter) , microsome , drug metabolism , kinetics , metabolism , transformation (genetics) , incubation , in vitro , organic chemistry , biochemistry , catalysis , physics , quantum mechanics , gene
In this study the comparison of human liver microsomes in in vitro incubation as well as ZnO‐ and TiO 2 ‐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.