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Analysis of In Vitro Mirtazapine Metabolites in Human Liver Microsomes by LC-HRMS
Ying Zhang1, Wen-Fang Zhang1, Duo-Qi Xu2
1Key Laboratory of Forensic Toxicology, Ministry of Public Security, Forensic Science Service of Beijing Public Security Bureau, Beijing 100192, China.
Objectives:
To establish and optimize an in vitro incubation system with human liver microsomes and investigate the in vitro metabolites and possible metabolic pathways of mirtazapine.
Methods:
Three major metabolites of mirtazapine were selected to optimize the incubation conditions of liver microsomes. The metabolites of mirtazapine were analyzed by liquid chromatography-high resolution mass spectrometry (LC-HRMS) to identify the in vitro metabolites and metabolic pathways of mirtazapine.
Results:
Ten metabolites, including nine phase Ⅰ metabolites and one phase Ⅱ metabolite, were identified in the in vitro liver microsome incubation. Among them, five new metabolites and one new metabolic pathway were discovered. The pathways involved in phase Ⅰ metabolic included methylation, hydroxylation, oxidation, reduction, etc., while the phase Ⅱ biotransformation was mainly glucuronidation.
Conclusions:
The metabolites discovered in this study are consistent with the main metabolites of mirtazapine reported in literature, which are N-desmethylmetazapine, 8-hydroxy mirtazapine and mirtazapine-N-oxide. The results can provide basis for the confirmation of mirtazapine cases and provide reference for the study of other substances.
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