Targeted and non-targeted metabolic analysis of chlorpromazine in grass carp as well as the in-silico and metabolomics toxicity assessment

Abstract

Chlorpromazine (CPZ) is an abused sedative that is extensively metabolized in organisms. However, the metabolic pathway of CPZ in aquatic organisms is still unclear. In this study, CPZ metabolites was analyzed in grass carp exposed to CPZ in the raising water using ultrahigh-performance liquid chromatography coupled with quadrupole Orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS). Thirteen CPZ metabolites were identified, including 11 previously reported and 2 newly identified metabolites (M9 and M13), and 5 known metabolites were confirmed using authentic standards. The molecular structures and transformation pathways of CPZ metabolites were putatively deduced, which mainly included oxygenation, demethylation, dechlorination and carboxylation reactions. Quantitative analysis of CPZ and its metabolites were also performed, and CPZ sulfoxide had a higher content as an important characteristic metabolite. In addition, in-silico toxicity prediction reminded that some metabolites possess ecotoxicity and developmental toxicities similar to, or even higher, than CPZ. Moreover, metabolomics results indicated that CPZ exposure could cause metabolic disorder in the endogenous metabolome of grass carp.