Surveillance assay development

The safe concentration of drug-related residue must be known in order to determine the withdrawal period for a veterinary product. Often the toxicity data is incomplete and an estimate must be made to progress with requisite residue studies. One approach is to conduct a total residue study with sufficiently widely-spaced sacrifice intervals to assess the rate of depletion of total residue over the projected range of probable safe concentrations. A zero-withdrawal sacrifice interval should be included. The target tissue and marker residue are identified and surveillance/confirmatory assays developed. If a major portion of residue is non-extractable (bound) and the marker is undetectable at times when total residue is still significant, a residue bioavailability study may be necessary. To complete the data package, final residue and comparative metabolism studies are conducted. Studies on the metabolism of flunixin in cattle will illustrate this approach. 

Following development of the assays for the marker residue (flunixin), liver tissue from feeder cattle dosed intravenously daily for three days with C-flunixin NHG (second total residue depletion study) was assayed by the surveillance method. Based on this assay, mean values of flunixin in the liver at 12 and 24 hours post final dose were 531 and 36 ng/g tissue, respectively. Liver samples collected at 72 and 120 hours contained flunixin concentrations below the limit of quantitation of the assay. The flunixin concentrations at.12 and 24 hours represented less than one-third of the total u residues, and although no fluni n was detected at 72 and 120 hours, there were still detectable residues at these sacrifice intervals. 

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