The metabolism of [14C]ceftiofur following intramuscular (im) administration to cattle and oral dosing in rats produced a single metabolite, desfuroylceftiofur, which was observed in the plasma of both species. Desfuroylceftiofur existed free in the plasma of cattle but was covalently bound to plasma proteins in rats. Urinary metabolites from both species appear qualitatively similar but quantitatively different depending on the dose, route of administration, and the time interval posttreatment. Most of the urinary metabolites in rats and cattle are derivatives of desfuroylceftiofur and are probably artifacts due to the ease of its oxidation in base, lactonization in acids, and hydrolysis of lactones. An interesting metabolite ceftiofur sulfoxide cysteine is the major metabolite in the urine of rats dosed orally at or above 100 mg/kg. However, it was not present at oral doses of 7-15 mg/kg nor after im treatment of cattle and rats.Ceftiofur (I-B, Table I) is very effective in control of Gram-positive and Gram-negative bacterial pathogens of veterinary importance both in vivo and in vitro (Yancey et al, 1986). Its sodium salt, NAXCEL, has recently been

A liquid chromatographic (LC) method has been developed for the determination of the desfuroylceftiofur metabolite of ceftiofur as a residue in the plasma of animals. Plasma sample in 0.1 M pH 8.7 phosphate buffer containing dithioerythritol is Incubated under nitrogen for 15 min at 50°C. The sample is centrifuged, charged to a C18 cartridge, and washed with 0.1M ammonium acetate. The desfuroylceftiofur residue on the cartridge Is derivatized by adding 0.1M ammonium acetate containing iodoacetamide and letting the cartridge stand in the dark for 30 min. The cartridge is then drained and rinsed, and the desfuroylceftiofur acetamide is eluted with methanol. The mixture is evaporated to dryness, dissolved in pH 10.6 sodium hydroxide, and charged to a SAX cartridge. The derivative is eluted with 2% acetic acid, reduced In volume, and dissolved in mobile phase for liquid chromatography. The LC system includes a C8 column and guard cartridge with UV detection at 254 nm. The gradient mobile phase (flow rate 1 mL/mln) is 0.01M pH 5 ammonium acetate programmed to 29 % methanol-water (60 + 40) in 25 min. Recoveries were 90-100% with a sensitivity of 0.1 ppm or less. The procedure has been applied to the plasma of cattle, rats, horses, pigs, and dogs.

Ceftiofur sodium, a new broad-spectrum cephalosporin, has been approved in the US, Canada, and several other countries throughout the world to treat bovine respiratory disease in cattle and dairy cows. In Experiment 1, 6 lactating cows were intramuscularly treated with 2.29 mg of [14C]ceftiofur/kg of BW daily for 5 d. In Experiment 2, 30 additional cows at three locations were similarly treated with 2.2 mg of ceftiofur (unlabeled)/kg of BW. Milk was collected every 12 and 24 h after each dose and every 12 h up to 5 d after the last dose. The majority of milk samples, both during treatment (12 and 24 h after each dose) and after the last dose (up to 5 d following ceftiofur treatment), were negative by screening procedures based on microbial inhibition (Delvotest-P, Bacillus stearothermophilus disk assay, and cylinder plate assays). The receptor-binding Charm Test II assay, which has a limit of detection of .005 ppm of ceftiofur, gave positive tests for milk samples up to 48 h following treatment. When the Charm Test II assay is used with .008 IU/ml of penicillin as a positive control, 44% of the samples from individual cows were negative at 12 h posttreatment. Ninety percent of the samples from individual cows were negative at 24 h after the last treatment. The use of ceftiofur in dairy cattle in accordance with the label directions does not result in total residues in milk higher than the FDA-calculated safe concentration of 1-ppm ceftiofur equivalents. The milk from individual cows did not test positive by the commercial screening assays examined in this study, except for the Charm Test II. The Charm Test II was 90% negative using the Charm Sciences criteria at 24 h after the last treatment.

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Seven laboratories collaboratively studied a method for the assay of melengestrol acetate at the 0, 10, and 20 ppb levels in bovine fat, liver, muscle, and kidney. The study included fortification of tissue by each laboratory and analysis of fat samples taken from treated heifers which had endogenous levels of 0, 10, and 20 ppb melengestrol acetate. The multistep cleanup procedure used included extraction, solvent partition, column chromatography, and electron capture gas-liquid chromatographic determination. Results of the study for muscle, liver, kidney, and fat showed that the method gave satisfactory recoveries and accuracy. In fat, the most critical tissue, recovery was >93%. A statistical comparison of the results reported for fat tissue from treated heifers demonstrated that 5 of the 7 laboratories obtained similar results. The results produced by the method can be expected to be repeatable within and among laboratories. On the basis of the collaborative results the method has been adopted as official first action.