Safety animal drug residue methods

Any effort to develop performance criteria for screening test for animal drug residues must have the twin goals of providing for good method performance and of not unnecessarily restricting the development and maturation of an analytical technology that has potential benefits for human food safety and public health. 

The most critical decision to be made is the choice of the best solvent to facilitate extraction of the drug residue while minimizing interference. A review of available solubility, logP, and pK /pKb data for the marker residue can become an important first step in the selection of the best extraction solvents to try. A selected list of solvents from the literature methods include individual solvents (n-hexane, " dichloromethane, ethyl acetate, acetone, acetonitrile, methanol, and water ) mixtures of solvents (dichloromethane-methanol-acetic acid, isooctane-ethyl acetate, methanol-water, and acetonitrile-water ), and aqueous buffer solutions (phosphate and sodium sulfate ). Hexane is a very nonpolar solvent and could be chosen as an extraction solvent if the analyte is also very nonpolar. For example, Serrano et al used n-hexane to extract the very nonpolar polychlorinated biphenyls (PCBs) from fat, liver, and kidney of whale. One advantage of using n-hexane as an extraction solvent for fat tissue is that the fat itself will be completely dissolved, but this will necessitate an additional cleanup step to remove the substantial fat matrix. The choice of chlorinated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride should be avoided owing to safety and environmental concerns with these solvents. Diethyl ether and ethyl acetate are other relatively nonpolar solvents that are appropriate for extraction of nonpolar analytes. Diethyl ether or ethyl acetate may also be combined with hexane (or other hydrocarbon solvent) to create an extraction solvent that has a polarity intermediate between the two solvents. For example, Gerhardt et a/. used a combination of isooctane and ethyl acetate for the extraction of several ionophores from various animal tissues. 

There has been an increasing worldwide public outcry to know what residues and contaminants are in the food supply, and a demand that food be free of residues that could have an impact on the public health. A simplistic but often voiced concept is that edible animal products should be only consumed when all administered drugs and drug-related residues have been totally eliminated. For some time in the past, this concept seemed to guarantee the highest degree of food safety as animal products destined for human consumption were found to be free of drug residues by the analytical methods applied at that time. 

Presently, some countries including the United States and a few Member States of the European Union use statistical methods to establish withdrawal periods. However, most countries employ a simple method the withdrawal period is set at the time point when residues in all tissues in all the animals have depleted to below the respective MRL values. When one has determined that time point, the estimation of a safety span also has to be considered in order to compensate for uncertainties of the biological variability. The dimensions of a safety span depend on various, not easy to specify, factors determined by the study design, the quality of the data, and the pharmacokinetic properties of the drug. Hence, an overall recommendation on the estimation of the safety span cannot be provided. An approximate guide for the safety span is likely to be a value of 10-30% of the time period when all observations are below the MRL. As an alternative, the safety span might be calculated from the tissue depletion curve as a value of possibly one to three times the half-life. 

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