Sulfonamides Sulfamethazine

A variety of procedures utilizing colorimetric, spectrophotometric, and isotopic techniques with several different drugs have been described for measuring N-acetyltransferase activity in vitro. Drugs which have been used include isoniazid, several sulfonamides (sulfamethazine, sulfadi-... 

Test strip and immunoflltration devices were developed by Ostermaier et al to detect sulfadiazine, sulfamethazine, and sulfamethoxypyridazine in milk. Direct competitive immunoassay was utilized with sulfonamide-horseradish peroxidase as the detector. The LOD for sulfamethazine for both the dipstick and immunoflltration was 10 pg kg for sulfadiazine, the LOD was 12 pg kg for the dipstick and 30 pg kg for immunoflltration. For sulfamethoxypyridazine, the LOD was 10 pgkg for the dipstick and 20 pgkg for immunoflltration. The devices were found to be suitable for on-site use with undiluted milk. 

The bioslurry treatment successfully removed several of the PhC to non-detectable levels after 26 days three histamine H2-receptor antagonists (ranitidine, famotidine, cimetidine), two (1-blockers (atenolol, sotalol), one barbiturate (butalbital) and one antidiabetic compound (glibenclamide). The elimination of the sulfonamide antibiotics sulfapyridine (100%), sulfamethazine (91.0%) and... 

Macrolide antibiotics (clarithromycin, dehydroerythromycin, etc.) and sulfonamides (sulfamethoxazole, sulfadimethoxine, sulfamethazine, and sulfathi-azole) are the most prevalent antibiotics found in the environment with levels around a few micrograms per liter, whereas fluoroquinolones, tetracyclines, and penicillins have been detected in fewer cases and usually at low concentrations (nanograms per liter) [3,20,23,72]. This result is not surprising, since penicillins are easily hydrolyzed and tetracyclines readily precipitate with cations such as calcium and are accumulated in sewage sludge or sediments. Several reviews have reported the environmental occurrence of different antibiotics in aquatic and soil compartments. Some of these data are detailed in Table 1. 

As occurred with the other antibiotics, commercial immunoassay formats, also available as kits for tetracyclines and penicillins such as the Parallux, the LacTek, or the Charm II, have also been placed on the market for the analysis of sulfonamides (see Table 4). Thus, the Parallux detects sulfamethazine and sulfadimethoxine in raw milk with a LOD of 10 pg L1. The Charm II detects almost all sulfonamides in honey and milk with a LOD in the range from 1 to 10 pg L, whereas LacTek is able to detect sulfamethazine. Moreover, the 5101SULlp and 5101SUDAlp tests reach LOD values for sulfamethazine and sulfadiazine of around 0.2 pg L 1 and they have been applied to the analysis of urine, milk, and plasma. These tests have proved to be efficient as a point of care for on-site applications on farms. Moreover, commercially available antibodies can be found from several sources such as Silver Lake Research, US Biological, Cortex Biochem. Inc., Accurate Chemical Scientific, Fitzgerald Industries International Inc., and Biotrend Chemikalien GmbH. 

We have found only one attempt to use immunoassays to detect sulfonamides in environmental samples. As in the case of penicillins and tetracyclines and also for fluoroquinolones (see below), Campagnolo et al. [84] measured sulfonamides in water samples proximal to a farm in Iowa using a commercial Charm II RIA test, accomplishing a LOD of 5 pg L 1 for sulfamethazine. 

Currently, the most widely used are sulfisoxazole, sulfamethoxazole, sulfadiazine, sul-famethizole, and trisulfapyrimidine (a mixture of sulfamerazine, sulfamethazine, and sulfadiazine). The first two drugs mentioned are the most widely used. The long-lasting sulfonamide (sulfadioxin) is used only in combination with pyrimethamine (an antagonist of folic acid) for prevention and treatment of tropical fever. 

Except for sulfonamides such as phthalylsulfathiazole and succinylsulfathi-azole, which are not absorbed from the intestine, most members of the sulfonamide group follow a common pharmacological pattern. Following oral administration, absorption rates of sulfonamides are approximately proportional to their water solubility although these can vary between species. Thus, pigs and horses absorb sulfonamides move slowly than birds but better than cattle. Exceptions are sulfapyridine, which is slowly absorbed in most species, and sulfamethazine, which is second to sulfanilamide in the rate of absorption. 

The absorption of sulfonamides by diseased animals may be quite different from that observed in healthy individuals of the same species. Experimental rumen stasis, produced by atropine, markedly reduced the absorption of sulfamethazine following its oral administration to sheep. 

The extent to which a sulfonamide is acetylated depends upon the drug administered and the animal species. Acetylsulfathiazole is the principal metabolite found in the urine of cattle, sheep, and swine after enteral or parenteral administration of sulfathiazole. However, sheep can acetylate only 10% of the dose, while cattle can acetylate 32%, and swine 39%. When sulfamethazine was administered intravenously or orally to cattle, the animals eliminated 11% or 25% of the dose, respectively, in urine as N" -acetylsulfamethazine. The increased acetylation that occurred following tlie oral administration may be related to the increased exposure of sulfamethazine to liver enzymes following its absorption into the portal circulation. The acetylation rate may also be affected by the health status of an animal. Tims, cows suffering from ketosis in cows acetylate sulfonamides at much lower extent. 

Oxidation of sulfonamide rings is another important metabolic process in certain species. Sheep eliminate 25% of an intravenous dose of sulfamethazine in... 

Sulfathiazole is available for oral use and is also included in some parenteral formulations in combination with other sulfonamides. It is also used as a feed additive for growth promotion purposes. It is more toxic than sulfamethazine and sulfadimethoxine but is safe when used as the phthalyl derivative. 

Antibiotics a, chiortetracyciine b, erythromycin c, gentamicin d, neomycin e, oxytetracycline t, penicillins g, streptomycin h, tetracycline i, tylosin j, chloramphenicol. Sulfonamides k, sulfabromomethazine I, sulta-chlorpyridazine m, sulfadiazine n, sulfadimethoxine o, sulfaethoxypyridazine p, sulfamethoxypyridazine q, sulfapyridine r, sulfamethazine s, sulfaquinoxaline t, sulfathiazole... 

Antibiotics a neomycin b tetracycline c streptomycin d penicillin e chlortetracycline f oxytetracycline g gentamicin h erythromycin. Sulfonamides sulfachlorpyridazine k sulfamethazine I sulfadimethoxine m sulfathiazole n sulfadiazine... 

In addition, a total of 14 sulfamethazine and 3 sulfadimethoxine violations occurred among 7824 samples from all slaughter classes monitored for sulfonamides, Bob calves exhibited four sulfonamides violations, sows and boar/stags three, and lambs and market hogs two. One sulfonamide violation was observed in each of non-formula-fed veal, goats, and geese. Swine exhibited 24 violative samples of 15,600 analyses in swine in 1996 violative levels of sulfadimethoxine were reported in the muscle of one animal. Violative levels of sulfamethazine were reported in the muscle of 15 animals, in the muscle and liver of 7 animals, and in the liver of 1 animal. 

Fru thermore, 156,078 samples from cattle, sheep/lambs, goats, swine, and other animals were screened for antibiotics and sulfonamide drug residues using the fast antimicrobial screen test (FAST) developed in 1991 to replace CAST and STOP. There were 1022 violations for cattle and 2 for swine samples. In cattle, violative cases included 335 for penicillin, 142 for streptomycin, 128 for tetracycline, 28 for erythromycin, 48 for neomycin, 174 for oxytetracycline, 17 for chlortetracycline, 109 for gentamicin, 87 for sulfamethazine, 22 for sulfamethoxazole, 141 for sulfadimethoxine, 7 for sulfachlorpyridazine, 2 for tylosin, and 19 for sulfathiazole. In swine, violative samples were limited to one for oxytetracycline and one for penicillin. Analogous surveys conducted in 1995 showed 804 violative specimens of the 68,139 samples tested. 

In addition, specific testing was performed for chloramphenicol in muscle, nitrofurans in muscle and serum, dimefridazole in muscle of pigs and poultry, and sulfonamides in liver. In Australia, chloramphenicol is not registered for use in food animals and nitrofurans are only available as a topical preparation for use in companion animals. No residues of either of these compounds were detected. No residues of dimefridazole were detected in pig and poultry samples. Sulfonamide residues were monitored in cattle and pigs. No residues were detected in 613 cattle samples. In 594 pig liver samples analyzed, 9 residues of sulfamethazine (sulfamethazine) were detected, 4 of which were above the MRL. 

In Poland, samples of muscle, kidneys, and liver from cattle, swine, horses, and poultry are taken four times per year by veterinary inspectors at slaughterhouses to be analyzed for drug residues. Between 1992 and 1996, 5733 samples of cattle, swine, horse, and chickens muscle were analyzed to determine residues of sulfonamides, nitrofurans, and nitroimidazoles 2613 samples of cattle and swine liver to determine -agonists and 1661 samples of cattle and swine kidney to determine violative levels of tranquilizers and -blockers. No residues of the mentioned groups of drugs above MRL were detected in the examined samples (42). However, nonviolative residues of sulfamethazine, sulfadimethoxine, sulfathiazole, furazolidone, nitrofurazone, nitrofurantoin, metronidazole, dimetridazole, azaperone, chlorpromazine, propiopromazine, carazolol, clenbuterol, and salbutamol could be detected in the corresponding target samples. 

In 1986, a monitoring program for potential presence of sulfonamide residues in food of animal origin was introduced in Slovenia (43). A total of 225 samples including muscle, liver, kidney, canned ham, egg, and milk were collected and analyzed. Results showed that only one canned ham sample was contaminated with sulfamethazine at a level of less than 50 ppb. 

The stability of sulfonamide residues in animal tissues during frozen storage has been investigated in several studies, most of which dealt with sulfamethazine (2,... 

Apart from sulfamethazine, the stability of several other sulfonamides including sulfathiazole, sulfachlorpyridazine, sulfaquinoxaline, and sulfadimethoxine in spiked pig liver frozen at 20 C have been investigated over a period... 

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