Drug residues

R. J. Heitzman, Veterinary Drug Residues. Residues in Food Producing Animals and their Products Reference Materials and Methods, Final Report EUR 14126EN, Office for Official Publications of the European Communities Luxembourg, 1992. 

Toxic compounds polychlorinated biphenyls, polycyclic aromatic hydrocarbons, organochlorine pesticides, chlorinated pesticides, dioxins, veterinary drug residues, hormone residues, aflatoxins, toxic compounds in shellfish. Compoimds of nutritional significance in foods vitamins, fat, lipids, carbohydrates, protein, energy-calorific value, proximates, dietary fibre, ash. Other compounds hormones in blood serum... 

The process of development and validation of animal drug residue methods for US Food and Drug Administration regulatory use... 

The US Food and Drug Administration (FDA) evaluates methods to be used in government regulatory laboratories for the determination and confirmation of drug residues in food derived from animal products. The FDA Center for Veterinary Medicine (CVM) oversees the validation (i.e., demonstration that the method is suitable for use) via a protocol known as a method trial. CVM ensures that the appropriate government laboratories have the tools needed to monitor the Nation s food supply. 

The FDA requires [FDC Act, Section 512 (b)(1)(G)] that methods used for the detection and confirmation of drug residues in animal products be practicable. Overseeing the reliability of these methods is the responsibility of the FDA CVM. The methods are corroborated using an interlaboratory evaluation of the method known as a method trial. The method trial is used to demonstrate that the method is suitable for use to detect and confirm drug residues and can be performed by a trained analytical chemist. 

A method should be able both to quantify the amount of marker drug residue present in the sample and to identify the compound unambiguously. Historically, this required two distinct procedures a determinative procedure used to quantify the analyte, and a confirmatory procedure used to unequivocally identify the analyte. The need for two procedures was driven by the limitations of available technology. Most determinative methods over the last two decades have been based on liquid chromatography, usually with ultraviolet (UV)/visible or fluorescence defection. Limitations of cost. 

Guidance for Industry No. 118 Mass Spectrometry for Confirmation of the Identity of Animal Drug Residues DRAFT GUIDANCE June6,2001, US Department of Health and Human Services, Public Health Service, Pood and Drug Administration, Center for Veterinary Medicine, RockvUle, MD (2001). 

Once the sample has been processed in such a way as to maintain residue stability, to prevent cross-contamination, and to ensure homogeneity, strategies to extract the drug from the tissue and to isolate the drug residue from potential interferences must be evaluated. The following sections will review these two concepts separately. 

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. 

N. Haagsma and C. van der Water, Immunochemical methods in the analysis of veterinary drug residues, in Analysis of Antibiotic Drug Residues in Food Products of Animal Origin, ed. V. K. Agarwal, Plenum Press, New York, pp. 81-97 (1992). 

Quantitative immunoassays have also been used as screening devices to determine whether drug residues exceed established maximum residue limits (MRLs) or tolerances in edible tissues. " For these applications, a cut-off value is set at the tolerance or MRL samples detected above this level are positive , and samples below this level are negative. ... 

S.F. Sundlof and J. Cooper, Human health risks associated with drug residues in animal-derived foods, in Veterinary Drug Residues, Food Safety, ed. W.A. Moats and M.B. Medina, American Chemical Society, Washington, DC, pp. 5-17 (1996). 

When pharmaceuticals are administered to feed animals there is a special concern about the possible accumulation of drug residues in the animals tissues. Thus, in these bioequivalency studies it may be appropriate to carefully monitor parameters that define possible tissue accumulation [45]. 

Cyanides, including metal-cyanide complexes Drug residues Chromium, cadmium, lead, mercury, nickel. dissolve material used in sealing a site... 

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