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

• Published in: Rapid communications in mass spectrometry 2013-06, Vol.27 (12), p.1287-1293
• Main Authors: Tarbin, J. A., Fussell, R. J.
• Format: Article
• Language: English
• Subjects: Animals; Antifungal Agents - analysis; Antifungal Agents - metabolism; Antifungal Agents - therapeutic use; Biomarkers - analysis; Biomarkers - metabolism; Cattle; Cattle Diseases - drug therapy; Cattle Diseases - metabolism; Chromatography, High Pressure Liquid - methods; Griseofulvin - analysis; Griseofulvin - metabolism; Griseofulvin - therapeutic use; Hair - chemistry; Hair - metabolism; Liquid chromatography; Liver - chemistry; Liver - metabolism; Markers; Mass spectrometry; Metabolites; Quadrupoles; Residues; Spectrometry, Mass, Electrospray Ionization - methods; Tandem Mass Spectrometry - methods; Veterinary Drugs - analysis; Veterinary Drugs - metabolism
• ISSN: 0951-4198; 1097-0231
• DOI: 10.1002/rcm.6574

RATIONALE 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. © Crown copyright 2013. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.