title: Identification of in vitro metabolites of a new anticoccidial drug nitromezuril using HepG2 cells, rat S9 and primary hepatocytes by liquid chromatography/tandem mass spectrometry.
abstract: BACKGROUND
  Nitromezuril is a novel triazine compound possessing remarkable anticoccidial activity that could have possible future use in the prevention of coccidiosis; however, its metabolic characteristics have still not been revealed.
  
  
  METHODS
  In the present study, the in vitro metabolism of nitromezuril in HepG2 cells, rat S9 and primary hepatocytes was investigated using high-performance liquid chromatography with electrospray ionization tandem mass spectrometry. The structures of metabolites and their product ions were easily and reliably characterized based on the accurate MS(2) spectra and known structure of nitromezuril.
  
  
  RESULTS
  As expected, three metabolites (M1-M3) were detected in a HepG2 cells system, one metabolite was respectively detected and identified as M1 in rat S9 and M2 in rat primary hepatocytes. M1 and M2 were confirmed respectively based on comparing their retention times, full scan, product ion scan with available authentic standards and M3 was tentatively identified as hydroxyl compound of M2.
  
  
  CONCLUSIONS
  Pathways of nitromezuril were reported for the first time and no obvious species difference was shown. The proposed metabolic pathways of nitromezuril can be expected to play a key role in pharmacodynamics and food safety evaluations.
authors: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, P.R. China.
authors: Keyu
authors: K
authors: Zhang
authors: Sumei
authors: S
authors: Li
authors: Wenli
authors: W
authors: Zheng
authors: Lifang
authors: L
authors: Zhang
authors: Chunmei
authors: C
authors: Wang
authors: Xiaoyang
authors: X
authors: Wang
authors: Chenzhong
authors: C
authors: Fei
authors: Feiqun
authors: F
authors: Xue
authors: Mi
authors: M
authors: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002853:Chromatography, Liquid / Q000379:methods*; D003049:Coccidiostats / Q000493:pharmacokinetics*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D051381:Rats; D013045:Species Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014227:Triazines / Q000493:pharmacokinetics*
chemical_list: C000588635:2-(3-methyl-4-(4-nitrophenoxy)phenyl)-1,2,4-triazine-3,5(2H,4H)-dione; D003049:Coccidiostats; D014227:Triazines