title: Metabolite profiling using liquid chromatography/quadrupole time-of-flight mass spectrometry for the identification of a suitable marker and target matrix of griseofulvin use in bovines.
abstract: BACKGROUND
  Griseofulvin is an antifungal agent with potential for misuse in food-producing animals. Little is known about its metabolism in ruminants and hence what are suitable marker residues and target matrices for monitoring purposes.
  
  
  METHODS
  Tissues harvested from cattle treated with the antifungal agent griseofulvin were screened using liquid chromatography coupled to positive and negative electrospray ionization (ESI) quadrupole time-of-flight mass spectrometry (qToFMS) operated in ToF mode.
  
  
  RESULTS
  Twenty-five possible metabolites were detected across all tissue types, but two isomeric compounds with accurate masses corresponding to loss of a methyl group from parent griseofulvin were considered to be the best candidate markers. Data from fragmentation experiments enabled a tentative assignment of the structures of the two compounds as 4-demethylgriseofulvin and 6-demethylgriseofulvin. These assignments were confirmed by matching the product ion spectra of incurred residues to those of custom synthesized reference standards.
  
  
  CONCLUSIONS
  4-Demethyl- and 6-demethylgriseofulvin have been identified as potential marker compounds of griseofulvin use in cattle. Liver was identified as the target matrix. Hair was shown to have potential for non-invasive testing.
authors.affiliation: Food and Environment Research Agency, York YO41 1LZ, UK. jonathan.tarbin@fera.gsi.gov.uk
authors.forename: J A
authors.initials: JA
authors.lastname: Tarbin
authors.forename: R J
authors.initials: RJ
authors.lastname: Fussell
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006118:Griseofulvin / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use; D006197:Hair / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D019155:Veterinary Drugs / Q000032:analysis* / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D015415:Biomarkers; D019155:Veterinary Drugs; D006118:Griseofulvin