Metabolites maximum residue limits

A unique feature of the development of veterinary medicines for food-producing species is the need to consider the establishment of Maximum Residue Limits (M RLs) for the drug or its metabolites in food produce. A MRL is defined in the European Union as ... 

Sulfonylurea herbicides are generally applied to crops as an early post-emergent herbicide. Crops that are tolerant to these herbicides quickly metabolize them to innocuous compounds. At maturity, residues of the parent compound in food and feed commodities are nondetectable. Metabolites are not considered to be of concern, and their levels are usually nondetectable also. For this reason, the residue definition only includes the parent compound. Tolerances [or maximum residue limits (MRLs)] are based on the LOQ of the method submitted for enforcement purposes and usually range from 0.01 to 0.05 mg kg (ppm) for food items and up to O.lmgkg" for feed items. There is no practical need for residue methods for animal tissues or animal-derived products such as milk, meat, and eggs. Sulfonylurea herbicides are not found in animal feed items, as mentioned above. Furthermore, sulfonylurea herbicides intentionally dosed to rats and goats are mostly excreted in the urine and feces, and the traces that are absorbed are rapidly metabolized to nontoxic compounds. For this reason, no descriptions of methods for animal-derived matrices are given here. 

Oxime carbamates are generally applied either directly to the tilled soil or sprayed on crops. One of the advantages of oxime carbamates is their short persistence on plants. They are readily degraded into their metabolites shortly after application. However, some of these metabolites have insecticidal properties even more potent than those of the parent compound. For example, the oxidative product of aldicarb is aldicarb sulfoxide, which is observed to be 10-20 times more active as a cholinesterase inhibitor than aldicarb. Other oxime carbamates (e.g., methomyl) have degradates which show no insecticidal activity, have low to negligible ecotoxicity and mammalian toxicity relative to the parent, and are normally nondetectable in crops. Therefore, the residue definition may include the parent oxime carbamate (e.g., methomyl) or parent and metabolites (e.g., aldicarb and its sulfoxide and sulfone metabolites). The tolerance or maximum residue limit (MRL) of pesticides on any food commodity is based on the highest residue concentration detected on mature crops at harvest or the LOQ of the method submitted for enforcement purposes if no detectable residues are found. For example, the tolerances of methomyl in US food commodities range from 0.1 to 6 mg kg for food items and up to 40 mg kg for feed items. ... 

The biotransformation of fenthion in animals and plants leads to five major metabolites. According to the FAO, the maximum residue limit in different commodities includes the sum of the active ingredient and the metabolites, expressed as fenthion. A satisfactory separation was achieved with an RP-18 column and UV determination (95). 

Within the EU, in contrast with other areas of food control, there is no obligation to use standardized methods in the surveillance of veterinary medicine residues. Instead, a criterion-based approach applies that defines the performance characteristics that the methods used must meet." However, within the United States and some other countries methods are statutorily prescribed. The method must be able to detect the marker residue, specifically, mefabolife, sum of metabolites, or parent compound at/or below the appropriate regulatory limit (RL), as available. In the EU, the RL for authorized veterinary medicinal products is the maximum residue limit (MRL). The RL for prohibited and unauthorized substances is the minimum required performance limit (MRPL) or the reference point for action (RPA). ° In other cases, especially for unauthorized substances, the Community Reference Laboratory (CRL) Recommended Concentration (RC)" can be applied, although this has no legal standing and is not a limit per se. 

With the extensive use of drugs in animal production, violative residues of the parent drugs and/or metabolites have a high potential to be present in meat, milk, eggs, and honey. The level of residues and the individual drugs they originate from determine the public health significance of such an adulteration of the food supply. The European Union (EU) and the Joint FAO/WHO Expert Committee on Food Additives (JECFA) have established maximum residue limits (MRLs) for several quinolones. 

Multiresidue methods are the most powerful procedures for the analysis of pesticides in environmental, food, and/or feed samples. The maximum residue limits of the pesticides prescribed by health authorities include not only the residues of the parent compounds but their toxic metabolites as well. There is also a trend toward inclusion of residues of highly polar and conjugated metabolites (126). The ever-increasing demands on the quality of food, feed, and environmental samples, and the lowering of the maximum residue limits, require the development of new and more sensitive methods. To distinguish the pesticide signals from the interfering coextractives of samples demands more selective detection. TLC methods alone are not sufficient and should be combined with GLC, HPLC, mass spectrometry, etc. 

Amounts of pesticides and their metabolites above their maximum residue limits (MRLs) in drinking waters and foods have pathogenic effects on humans and animals. This has raised the need for fast, sensitive methods for the routine analysis of various classes of pesticides in environmental and physiological matrices. It is especially important to control the contaminant levels in foodstuffs and also of envirorunental (surface, groimd)... 

Of all the systems which have been utilized for the analysis of pesticide residues, combined gas chromatography-mass spectrometry afiFords a particularly useful approach because positive identification of the components of a mixture can be made without prior separation at sensitivities compatible with the limited quantities of residues generally available. From the results of recent studies involving the application of this technique, it has been demonstrated that available residue analytical methods provide efficient isolation and adequate cleanup of extracts of human, animal, and environmental media in most cases to permit gas chromatographic-mass spectrometric analyses with maximum confidence. Additionally, it has been shown that this combined technique will conveniently provide definitive and conclusive confirmation of residue identity as well as characterization of residues and their metabolites of unknown structure. 

For maximum precision and reproducibility, we found that it was necessary to incubate the standards and unknowns with the MAb for at least 2 hr at room temperature before the mixtures were added to the coated EIA wells. The dose-response curve of the EIA was between 1 and 100 ppb for ivermectin, abamectin, and the other analogs and metabolites described below. We did not determine the ultimate detection limits of the procedures for abamectin residues in water or strawberry homogenate. However, we recovered as little as 0.1 ppb of abamectin in water with s90% efficiency by the procedure described. The assay is extremely economical each sample well is coated with ivermectin-carrier conjugate containing about 25 ng of carrier protein, and each sample requires only 0.5 to 1 pi of MAb in filtered hybridoma culture medium. 

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