Comparison of the oral bioavailability and tissue disposition of monensin and salinomycin in chickens and turkeys.

The current study describes the pharmacokinetic parameters of two carboxylic polyether ionophores: monensin in turkeys and salinomycin in chickens. These data can be used to understand and predict the occurrence of undesirable residues of coccidiostats in edible tissues of these animal species. Special attention is paid to the distribution of residues between the different edible tissues during and at the end of the treatment period. For the bioavailability studies, monensin was administered to turkeys intravenously, in the left wing vein, at a dose of 0.4 mg /kg and orally at a dose of 20 mg /kg. Salinomycin was administered to chickens intravenously, in the left wing vein, at a dose of 0.25 mg /kg and orally at a dose of 2.5 mg /kg. Residue studies were carried out with supplemented feed at the rate of 100 mg /kg of feed for monensin in turkeys and 70 mg /kg for salinomycin in chickens, respectively. Coccidiostats had a low bioavailability in poultry (around 30% for monensin in chickens, around 1% for monensin in turkeys and around 15% for salinomycin in chickens). Monensin in chickens had a longer terminal half-life (between 3.07 and 5.55 h) than both monensin in turkeys (between 1.36 and 1.55 h) and salinomycin in chickens (between 1.33 and 1.79 h). The tissue /plasma partition coefficients showed a higher affinity of both monensin and salinomycin for fat, followed by liver and muscle tissue. The depletion data showed a fairly rapid elimination of coccidiostats in all the tissues after cessation of treatment. According to the results of depletion studies, a withdrawal period of 1 day seems sufficient to avoid undesirable exposure of consumers.

High-performance liquid chromatographic method with fluorescence detection for the screening and quantification of oxolinic acid, flumequine and sarafloxacin in fish.

A previously published liquid chromatographic method for determining residues of nine quinolones in chicken, porcine, bovine and ovine muscle was adapted and applied to fish tissue for simultaneous determination of three quinolones (flumequine, oxolinic acid and sarafloxacin). The analytes were extracted from homogenised muscle using an acetonitrile basic solution. After centrifugation, partial evaporation and cleaning with hexane, direct injection was possible. Separation was achieved on PLRP-S column and detection was performed with a programmable fluorescence detector. Chromatographic conditions were optimised to be compatible with the determination of the three quinolones in a single run. The linearity, recovery, accuracy and precision of the method were evaluated from fortified tissue samples at concentration levels ranging from 15 to 120 microg kg(-1) for sarafloxacin and 75 to 600 microg kg(-1) for oxolinic acid and flumequine according to the EU maximum residue limit of each quinolone. The limits of detection were estimated to be 2, 5 and 7 microg kg(-1), respectively, for sarafloxacin, oxolinic acid and flumequine. The limits of quantification were validated at 15 microg kg(-1) for sarafloxacin and 75 microg kg(-1) for oxolinic acid and flumequine. Mean extraction recoveries of quinolones in fish ranged from 56.9 to 71.0%. This simple and rapid method is suitable for residue control.

Sulphonamide residues in eggs following drug administration via the drinking water.

The aim was to determine concentrations of sulphadimidine (SDM) and sulphadimethoxine (SDT) in eggs following oral administration through drinking water for 5 days (0.5 g l(-1) for SDT, 1 and 2 g l(-1) for SDM). Residues of sulphonamides in albumen and yolk were monitored by high-performance liquid chromatography with UV detection. The limit of quantification was 0.005 microg g(-1) for the two egg components. The results indicate that 0.9-1.4% of the dose administered was deposited in eggs. Maximum concentrations in albumen were much higher than those in yolk. More than 75% of the overall sulphonamides detected in eggs was concentrated in the albumen. The residue levels declined below the limit of quantification within 12-20 days for albumen and 14-15 days for yolk after treatment was discontinued.

Elimination of oxolinic acid in eggs after oral treatment of laying hens.

1. Oxolinic acid is often used in poultry as a therapeutic agent. The aim of this study was to determine both its elimination into eggs, following oral dosing through the drinking water (12 mg/kg/d) or diet (13 mg/kg/d) for 5 d and its plasma concentrations. 2. Samples (albumen, yolk, plasma) were analysed by high performance liquid chromatography (HPLC) with fluorimetric detection. The limits of quantification were 10 ng/g in plasma and 5 ng/g in albumen and yolk. Residues were much higher in albumen than in plasma, whereas they were lower in yolk. 3. 95% of the overall oxolinic acid detected in eggs was concentrated in the albumen. 4. Detectable residues persisted for 9 d and 7 d, respectively, in albumen and yolk after the treatment was discontinued.

Multiresidue method for the determination of avermectin and moxidectin residues in the liver using HPLC with fluorescence detection.

A method using high-performance liquid chromatography (HPLC) and fluorescence detection is presented for the simultaneous determination of the antiparasitic agents avermectins (abamectin, ivermectin and doramectin) and moxidectin in liver. Samples are extracted using acetonitrile and cleaned up using solid phase extraction on a C18 column, followed by derivatization with trifluoroacetic anhydride. The samples are injected without further cleanup into the HPLC column and any avermectins or moxidectin present are detected using fluorescence detector set at 361 nm excitation and 465 nm emission wavelengths. The limits of quantification are below the stipulated EU Maximum Residue Limit for each of the avermectins and moxidectin. Mean recoveries in bovine liver ranged from 77.5 to 90.8%, with a RSD from 2.7 to 7.7%. The procedure provides a rapid, reliable and sensitive method for determinating avermectin and moxidectin residues in liver of different species (cattle, sheep, pigs). It is also applicable to muscle without modification.

Results of a European interlaboratory study for the determination of oxytetracycline in pig muscle by HPLC.

An interlaboratory study was organised in 1996 in order to determine laboratory testing performance for measuring oxytetracycline (OTC) and 4-epioxytetracycline (4-epiOTC) residues in pig muscle. The organisation was designed according to the 'International Harmonised Protocol for Proficiency Testing of (Chemical) Analytical Laboratories' produced by the Association of Official Analytical Chemists (AOAC International) and the International Union of Pure and Applied Chemistry (IUPAC). Fourteen National Reference Laboratories (NRLs) out of the 15 asked to participate agreed to analyse the samples. These laboratories were from 13 different European Union (EU) Member States and each participant was allowed to use the extraction method of their own choice but had to use liquid chromatography as the analytical technique. Most of the methods used were based on UV detection (simple wavelength or diode-array detection) but some involved fluorimetric detection. The production of incurred samples was prepared on-site. The OTC and 4-epiOTC concentrations present in the samples were determined by taking the mean of the results (excluding outliers) and the deviation of each result from the assigned value was measured. The performance of the laboratories was evaluated by calculating the 'z-scores'. The results were globally satisfactory and showed that all 14 laboratories were capable of determining OTC and 4-epiOTC in pig muscle with satisfactory accuracy. Only two laboratories obtained a questionable result in terms of repeatability.

Sulphonamide and dapsone residues in bovine milk following intramammary infusion.

The elimination into bovine milk of sulphonamides (sulphadimidine and sulphamethoxypyridazine) and dapsone following intramammary infusion was studied. Determination of sulphonamides and dapsone in milk was performed by a high performance liquid chromatographic method with UV detection. The limit of quantification was 0.01 microgram/ml. Withdrawal times were established considering the maximum residue limits fixed by the European Community (100 micrograms/kg for sulphonamides and 25 micrograms/kg for dapsone). The diffusion of residues into milk from a quarter infused by the intramammary route to the untreated quarters was also studied.

Residues of macrolide antibiotics in eggs following medication of laying hens.

1. The elimination kinetics of four macrolide antibiotics (tylosin, erythromycin, spiramycin and josamycin) in eggs were determined separately for albumen and yolk after oral administration through either drinking water or diet or after intramuscular injection. 2. Residues were assayed by a plate diffusion technique in cylinders with Micrococcus luteus as the test-organism. 3. Drug excretion was usually over a longer time in the yolk. Spiramycin was the most highly excreted in the egg whereas seven to eight times less tylosin and erythromycin was transferred. The conditions for the use of macrolide antibiotics in laying hens are discussed.

Sulphonamide residues in milk of dairy cows following intravenous injection.

An investigation was conducted into the elimination into milk of four sulphonamides (sulphadimidine, sulphamethoxypyridazine, sulphadimethoxine and sulphadoxine) after intravenous injections of drugs available in France. Sulphonamide determination in milk was performed using a high-performance liquid chromatography (HPLC) method with detection limit of 0.01 micrograms/ml. These results were used to determine the withdrawal times (two to six milkings) required for these drugs with a tolerance of 0.1 micrograms/ml as proposed by the European countries.

Depletion of colistin in eggs following medication of laying hens.

The depletion of colistin in eggs was determined separately for the albumen, the yolk and the whole egg after oral and intramuscular administrations of colistin sulphate. Residues were assayed by an agar plate diffusion method with Bordetella bronchoseptica ATCC 4617 as test organism. Colistin residues were not detected after drug administration by the oral route, but could be detected in the yolk until eight days after intramuscular injection. The total amount excreted represented 0.9% of the dose applied.

Residues of aminoglycoside antibiotics in eggs after medication of laying hens.

1. The transfer of aminoglycoside antibiotics into eggs was determined separately from albumen, yolk or whole egg after oral administration of dihydrostreptomycin (DHS), neomycin and spectinomycin and after an intramuscular injection of DHS. Residues were assayed by an agar plate diffusion method in cylinders with a specific test organism for each antibiotic. 2. Only DHS, administered by the intramuscular route, led to detectable residues in eggs. The total amount of DHS excreted via the eggs represented 1% of the dose administered. 3. Residues in the whole egg were detected for 8 d.

Excretion of tetracycline and chlortetracycline in eggs after oral medication of laying hens.

After dosing laying hens orally with tetracycline (TC) through either drinking water (0.25 and 0.5 g/l for 5 days) or feed (300 and 600 ppm for 7 days), and chlortetracycline (CTC) through feed (600 ppm) residues were determined by an agar plate diffusion technique in cylinders with Bacillus cereus as test-organism, separately for albumen and for yolk. The sensitivity threshold was 0.07 micrograms/g in albumen and 0.15 micrograms/g in yolk for TC and 0.01 micrograms/g in albumen and 0.06 micrograms/g in yolk for CTC. Drug excretion via egg was 3-fold higher for TC than for CTC. The drug was excreted preferentially into the yolk (about 75% of the total amount) and the elimination period lasted between 6 and 11 days for TC and 9 days for CTC, after treatment. Tetracycline use in laying hens is discussed, taking into consideration the proposals presented by the joint FAO/WHO Expert Committee on Food Additives.

Excretion of oxytetracycline in eggs after medication of laying hens.

The kinetics of oxytetracycline elimination into eggs were determined separately for albumen and yolk after oral administration through either drinking water (0.1-0.25 and 0.5 g/l for 5 days) or feed (300 and 600 ppm for 7 days) or after intramuscular injections (3 X 15 mg/kg body weight and 3 X 30 mg/kg body weight), 24 hours apart. Residues were assayed by a microbiological agar diffusion method, with Bacillus cereus as test-organism. The detection threshold was 0.07 micrograms/g for albumen and 0.2 micrograms/g for yolk. In all cases, the elimination period lasted longer for the yolk; it varied between 0 and 10 days after treatment was discontinued, according to administration routes and dosages. The conditions of oxytetracycline utilization in laying hens are discussed. The oral route only might be used to adhere to the proposals presented by the Joint FAO/WHO Expert Committee on Food Additives.