A field trial was set up to compare depletion of Brilliant Blue F.C.F., penicillin and dihydrostreptomycin following three infusions of Streptopen cerate 100 to six cows with experimentally induced staphylococcal mastitis. The presence of dye was noted by milk color at the time of milking, and by the ion exchange resin method in the laboratory. Penicillin residues were determined by a diffusion agar plate microbiological method using Sarcina lutea and by Delvotest P. Dihydrostreptomycin residues were measured by the diffusion agar plate method (Bacillus subtilis). Dye extinction times were found to be significantly longer than penicillin and dihydrostreptomycin extinction times in both the infected sides and the healthy sides. No significant differences were observed between healthy and infected sides for dye, penicillin or dihydrostreptomycin extinction.
A liquid chromatographic method was used to monitor a depletion study of carbadox (and its most important metabolite, desoxycarbadox) in young pigs fed carbadox-treated rations for 1 week. Carbadox was found in blood (20 ppb), blood serum (26 ppb), and muscle tissue 24 h after withdrawal from treated ration; residues were reduced to a trace (< 2 ppb) in 48 h, and eliminated by 72 h. Desoxycarbadox, although not detected in blood, was found in muscle (17 ppb) 24 h after withdrawal; it was reduced to 9 ppb at 48 h and to a trace by 72 h. Although no carbadox was detected in liver 24 h after withdrawal, appreciable desoxycarbadox (125 ppb) was found in liver 24 h after withdrawal; it was reduced to 17 ppb at 48 h and to a trace by 72 h. Whereas only a trace of carbadox was found in kidney 24 h after withdrawal, 186 ppb desoxycarbadox was found in kidney at 24 h, 34 ppb at 48 h, and a trace at 72 h. No metabolite of carbadox other than desoxycarbadox was found in extracts of swine tissues during this medicated feed trial, and no metabolite was found in blood extracts by using the established 'methodology. The effect of tissue storage (aging) at - 20°C on levels of the drug and its metabolite was a modest alteration of residue levels. The inadvertent use of feed adulterated with furazolidone and initially medicated with chlortetracycline, sulfamethazine, and penicillin G, did not affect the uptake of carbadox in this depletion study or interfere ) with the analytical methodology.
A study was conducted to monitor the elimination of dimetridazole (DMZ) and its major metabolite 2-hydroxymethyl-l-methyl-5-nitroimidazole (HMMNI) in swine plasma and tissue, using a liquid chromatographic method with electrochemical detector sensitive to 0.5 ppb. The study consisted of 2 experiments. In the preliminary experiment, one young female piglet was fed medicated ration containing 125 ppm dimetridazole (DMZ) for 2 weeks, followed by a withdrawal period using regular ration for 5 days. Another, control, piglet was given regular diet throughout. Plasma concentrations of DMZ and its most important residue, HMMNI, were measured daily at 2 h after the morning feeding and, on days 8 and 15, several times during the day. The 2 h concentrations after 3 days loading ranged from 47 to 77 ppb for DMZ and 424 to 1081 ppb for HMMNI. A daily cycle in the plasma levels was seen for both substances. Upon withdrawal of medication, elimination of drug and metabolite was biexponential with a terminal half-life of 6.7 h. In the second experiment, 5 piglets were medicated as above and slaughtered 2, 6, 12,25, and 49 h after withdrawal of the medication; the concentration of DMZ and HMMNI was measured in plasma, muscle, kidney, and liver. DMZ in the plasma amounted to 22 and 1.8 ppb at 2 and 6 h, while HMMNI declined from 535 ppb at 2 h to 0.75 ppb at 25 h. Most values for both substances found in muscle were close to those in the plasma; in kidney they amounted to 9-17% of the plasma levels. Very little HMMNI and no DMZ was found in the liver at 2 h. No drug or metabolite could be detected at 49 h in any of the tissues studied
A liquid chromatographic method with electrochemical detection in the reduction mode has been adapted for the estimation of furazolidone in pig tissues at residue levels. Chromatography of standard solutions shows good linearity from 0.2 to at least 10 ng injected. The limit of quantitation in spiked blank muscle and plasma is 0.5 ppb with 70% recovery and coefficients of variation ranging from 3.7 to 8.7%. In plasma, the concentration remains unchanged for up to 4 weeks at -30 "C, but the drug disappears rapidly from muscle both a t room temperature and a t -30 "C. Heat inactivation of spiked muscle by microwave increases the stability on storage. After the medicated diet is fed to pigs (330 ppm), the drug accumulates rapidly in plasma, reaching steady-state concentrations of approximately 500 ppb within '/z h, but drops overnight to below the limit of detection (0.2 ppb). The concentration in the muscle is @bout 3-6 times lower than in plasma. Depletion from both tissues occurs with a half-life of approximately 2 h. Furazolidone is not detected in liver and kidney at any time.Furazolidone [N-(5-nitro-2-furfurylidene)-3-amino-2-oxazolidone] is a veterinary drug widely used as an aid in the treatment of enteritis in swine. Administration is oral, either as a suspension or in feed a t a level of 330 ppm of complete feed.Various toxic effects from the use of furazolidone have been reviewed (Ali, 1983), and suspected toxicity in pigs, evident as a nervous syndrome, has been reported (Borland, 1979). Reference has been made to carcinogenicity in mice and rats after long-term administration (Ali, 1983) and to high mutagenic activity employing Salmonella (McCalla and Voutsinos, 1974). In view of these toxic effects, the possibility of residues of the drug or its metabolites in meat for human consumption is a major concern.Studies using 14C-labeled furazolidone in swine have indicated that the main excretion pathway for this drug is the urine (Vroomen et al., 1986b;Tennent and Ray, 1971). The half-life appears to be 2.6 h after a single dose, but radioactivity can still be detected in muscle tissue after 14 days. Feeding trials in swine using unlabeled drug (Winterlin et al., 1984;Vroomen et al., 1986b) have also confirmed that unchanged furazolidone is rapidly depleted from tissues. No furazolidone residue was found in muscle tissue by methods sensitive to 0.5 ppb.A method has recently been developed in our laboratory for the assay of dimetridazole residues and its metabolites in swine tissues and plasma at 0.5 ppb (Carignan et al., 1988a,b). This method is applicable with minor variations to other nitro compounds, including furazolidone. The preliminary studies reported here were undertaken to verify the usefulness of this method in determining the elimination of furazolidone after oral adminstration in feed at the recommended dose level of 330 PPm. MATERIALS AND METHODSChemicals and Supplies. Furazolidone was obtained from Sigma. Acetonitrile was HPLC grade (Baker). Water was purified by the Milli-Q four-bowl system...
Concentrates, one consisting primarily of oats The calcium content of milk was significantly and the other barley, were fed ad libitum to greater (P < 0.05) when the barley-based cows or at the rate of I kg per 3 kg of milk compared with the oat-based concentrate was yield for an entire lactation. Calcium, potas-fed. The sodium content of milk from cows sium, magnesium and sodium content of the fed concentrate ad libitum was sipificantly milk and milk yield were measured monthly. higher than from cows fed restricted amounts Potassium conti:nt and milk yield decreased of concentrate, Ayrshire milk was signifiand sodium content increased significantly cantly greater (P < 0.05) in magnesium con-(P < 0.05) with advancing stage of lactation. centration than Holstein milk.
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