Eleven new metabolites of fluvoxamine detected in the solid tissues and body fluids obtained from a deceased overdosed with fluvoxamine in vivo, and the metabolites in the human liver microsomes in vitro using LC-HR-MS/MS.

Purpose: Fluvoxamine (FLV) has been used widely as an antidepressant agent belonging to the group of second-generation selective serotonin reuptake inhibitors. However, only one work on the human metabolism of FLV was reported in 1983, examining a human urine specimen, and tentatively identified nine metabolites. Therefore, in the present work, the metabolites of FLV were examined in the liver, bile, and urine from a human cadaver, and the metabolites produced in the human liver microsomes (HLMs) in vitro were also examined.

Methods: Metabolites in each matrix were treated altogether in a tube where impurities had been precipitated using acetonitrile. The identification and tentative quantification of metabolites in human specimens and HLMs were performed using liquid chromatography (LC)-high resolution mass spectrometry (MS), LC-tandem mass spectrometry (MS/MS) and LC-QTRAP- MS/MS.

Results: Eleven new metabolites designated as M1 to M11 were detected from human cadaver specimens and HLMs. M1 was produced after acetylation at the terminal NH of FLV and was the most abundant metabolite in the liver and bile, but was the third abundant one in urine. M4 was produced after demethylation at the methoxy moiety of FLV, and was the most abundant metabolite in HLMs.

Conclusions: To our knowledge, this is the first report on the existence of eleven new metabolites (M1-M11) of FLV in HLMs, human liver, bile and urine. The present eleven metabolites may be useful for the identification of FLV in human samples both antemortem and postmortem.