Screening and confirmatory analyses of flunixin in tissues and bodily fluids after intravenous or intramuscular administration to cull dairy cows with or without lipopolysaccharide challenge

Authors: Shelver, Weilin; Smith, David; TELL, LISA - University Of California; BAYNES, RONALD - North Carolina State University; SCHROEDER, J - North Dakota State University; RIVIERE, JIM - Kansas State University

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/6/2015
Publication Date: 1/13/2016
Publication URL: https://handle.nal.usda.gov/10113/62183
Citation: Shelver, W.L., Smith, D.J., Tell, L.A., Baynes, R.E., Schroeder, J.W., Riviere, J.E. 2016. Screening and confirmatory analyses of flunixin in tissues and bodily fluids after intravenous or intramuscular administration to cull dairy cows with or without lipopolysaccharide challenge. Journal of Agricultural and Food Chemistry. 64(1):336-345. doi: 10.1021/acs.jafc.5b04793.

Interpretive Summary: Flunixin is an anti-inflammatory drug used to treat symptoms associate with mastitis or respiratory diseases in cattle. Regulatory agencies have often found tissue flunixin residues exceed the maximum allowable level but the exact reason for these violations is unknown. We hypothesized that pre-slaughter fluids might reflect tissue flunixin residues and that residue correlations between tissues and pre-slaughter fluids might be useful in identifying violative animals prior to slaughter. The determination of flunixin in tissues, milk, plasma, oral fluid, and urine using rapid screening assays were compared with instrumental analysis methods. The rapid screening method worked well for liver, kidney, and muscle confirmed by the instrumental method. Oral fluid levels did not correspond to flunixin levels in other tissues and could not be used to detect violative levels. The results showed no clear relation of flunixin levels to dosage route, but administration of bacteria toxin showed potential changes in the metabolism of flunixin which possibly might be related to the need for increased withdrawal times.

Technical Abstract: Twenty cull dairy cows (645 ± 83 kg) were treated with 2.2 mg/kg bw flunixin by intravenous (IV) or intramuscular (IM) administration with, or without, exposure to lipopolysaccharide in a two factor balanced design. The usefulness of screening assays to identify violative flunixin levels in a variety of easily accessible ante-mortem fluids in cattle was explored. Two animals with violative flunixin liver residue and/or violative 5-hydroxy flunixin milk residues were correctly identified by a flunixin liver ELISA screen. Oral fluid did not produce anticipated flunixin concentration profiles using ELISA determination. One cow that had liver and milk violative residues, and one cow that had a milk violation at the prescribed withdrawal period were correctly identified by flunixin milk lateral flow analyses. The ratio of urinary flunixin and 5-hydroxy flunixin may be useful for predicting disruption of metabolism caused by disease or other factors potentially leading to violative liver flunixin residues.