Residue depletion of amoxicillin and its major metabolites in eggs

The depletion of amoxicillin (AMO) and its major metabolites, amoxicilloic acid (AMA) and amoxicillin‐diketopiperazine‐2′,5′‐dione (DIKETO) in the albumen, yolk and whole egg was studied after the oral dose of AMO (25 and 50 mg/kg body weight) to laying hens once per day for five consecutive days. Egg samples were prepared by a simple liquid–liquid extraction procedure with acetonitrile and saturated methylene chloride and analysed using liquid chromatography–tandem mass spectrometry. The results showed that AMO, AMA and DIKETO residues were mainly distributed in the yolk, where particularly high concentrations of AMO and DIKETO were found, whereas the albumen contained high concentrations of AMA. This distribution suggested that AMO and DIKETO were depleted slowly in yolk, whereas AMA was depleted slowly in albumen. The amount of AMO residue positively correlated with the dose, and the theoretical withdrawal times, which were calculated based on the residue level falling below a safe limit, were 5.21 and 7.67 days at AMO doses of 25 and 50 mg/kg, respectively. Moreover, the theoretical withdrawal times for all residues in the whole egg were 8.00 and 9.11 days at doses of 25 and 50 mg/kg, respectively. Our findings suggested that 9 days was an appropriate withdrawal time for the use of AMO in laying hens.     

Residue depletion of thiamphenicol in the sea-bass

The residue depletion of thiamphenicol (TAP) was investigated in the sea-bass (Dicentrarchus labrax) after 5 days' treatment with medicated food at a dose of 15 or 30 mg/kg bw/day. Fish were sampled for blood and muscle + skin from 3 h until 14 days after treatment. Thiamphenicol concentrations were assayed by high performance liquid chromatography. Thiamphenicol concentrations measured 3 h after stopping treatment were 0.77 microg/mL and 0.91 (15 mg/kg dose) or 1.32 microg/mL and 1.47 microg/g (30 mg/kg dose), in plasma and muscle + skin, respectively. After a withdrawal of 3 days, plasma and tissue concentrations were: 0.08 microg/mL and 0.03 microg/g (lower dose) or 0.12 microg/mL and 0.06 microg/g (higher dose), respectively. Thiamphenicol was not detectable either in plasma or in tissues on days 7, 10 and 14 following withdrawal of the medicated food. Based on maximum residue levels (MRL) for TAP in fin fish, established at 50 microg/kg for muscle and skin in natural proportions, a withdrawal period of 5 and 6 days is proposed, after treatment at 15 or 30 mg/kg of TAP with medicated feed pellets, respectively, to avoid the presence of violative residues in the edible tissues of the sea-bass.     

替米考星预混剂在肉鸡体内残留消除规律的研究

替米考星为半人工合成的新型动物专用广谱抗生素。其具有左旋和右旋两种异构体，比例为85：15，具有较广的抗菌活性和较小的MIC，对许多革兰氏阳性菌和部分革兰氏阴性菌、支原体、螺旋体等有抑制作用，尤其对胸膜肺炎放线杆菌、溶血性巴氏杆菌、多杀性巴氏杆菌和支原体具有较强的抗菌活性。在我国已被允许作为治疗猪和牛的巴氏杆菌病和鸡的支原体感染。替米考星预混剂由于使用方便，已广泛应用于临床治疗。但如果使用不当，会造成药物残留。为了对其在肉鸡体内的残留消除进行了解，以便更好地使用该药防治动物疾病，同时为制定对人类安全的休药期提供可靠的依据，特进行了本次试验。     

Kinetic modelling and residue depletion of drugs in eggs

1. A physiologically-based pharmacokinetic model was developed for the purpose of describing the relationship between plasma concentration of drugs and their deposition into eggs. 2. By incorporating the physiology of egg formation into the model, the transfer of drugs into the egg albumen and yolk could be described using rate constants. 3. The model was used to describe concentrations in albumen and yolk of sulphanilamide, sulphaquinoxaline and pyrimethamine as a function of time using datasets from the literature. 4. The model could be used as a tool to obtain an insight into those properties of a drug which are responsible for the amount of residue in eggs, and could help in the design of critical studies for determining withdrawal periods for eggs.     

Residue depletion of decoquinate in chicken tissues after oral administration

Wang, Z.‐Y., Cai, C.‐Y., Chang, X.‐H., Fei, C.‐Z., Qiu, M.‐Q., Jiang, S.‐X., Xue, F.‐Q., Zhang, L.‐F. Residue depletion of decoquinate in chicken tissues after oral administration. J. vet. Pharmacol. Therap.  36 , 116–121. A rapid, sensitive, and reliable high‐performance liquid chromatography tandem mass spectrometry (LC‐MS/MS) method was developed and validated for the analysis of decoquinate in chicken tissues. The compounds were extracted using acetonitrile by liquid–liquid extraction (LLE) and purified with an Oasis^? HLB solid‐phase extraction (SPE) cartridge. Chromatographic separation was performed on an XTerra C₁₈ reversed‐phase column with a mobile phase of water containing 0.1% formic acid and acetonitrile. The analyte was detected by tandem quadrupole mass spectrometry after positive electrospray ionization by multiple reaction monitoring. The detection and quantitation limits were 1 and 2.5 μg/kg, respectively. The recoveries of edible tissues ranged from 85.3% to 104.9%, with relative standard deviations (RSD) lower than 10.4%. The depletion profile of decoquinate was studied in healthy chickens after oral administration of feed containing 27.2 mg/kg decoquinate for 10 consecutive days. The residue concentrations of decoquinate in chicken muscle and liver were detected using the developed method. The highest residue concentrations were attained 0.25 day post‐treatment, and decoquinate residues were still detected 5 days postmedication in the tissues examined. The developed method has been successfully applied to the depletion study of decoquinate in chicken tissues. The recommended withdrawal period with oral administration based on our research is 3 days.     

高效液相色谱荧光检测法检测鸡蛋中氨苄西林残留

鸡蛋经乙腈提取,饱和二氯甲烷萃取,水杨醛酸性条件下沸水浴衍生后,以0.01mol.L-1的磷酸二氢钾溶液（A）和乙腈溶液（B）为流动相,流速为1.0mL.min-1,荧光检测激发波长为354nm,发射波长为445nm,建立了用高效液相色谱荧光法检测鸡蛋中氨苄西林残留的方法。氨苄西林在5.0～800.0μg.L-1,本方法线性关系良好,相关系数为0.999 4。当氨苄西林添加水平为5～125ng.g-1时,该方法平均回收率为78.30%～85.11%,相对标准偏差为4.99%～7.25%;日内相对标准偏差为7.99%～9.64%;日间相对标准偏差为8.69%～12.48%。氨苄西林检测限为0.4ng.g-1（S/N=3）,定量限1.5ng.g-1（S/N=10）。所建立的方法简便、快速、灵敏度高,适用于鸡蛋中氨苄西林残留的高灵敏度检测。     

Study of enrofloxacin and flumequine residues depletion in eggs of laying hens after oral administration

Two groups of laying hens (each n=12) were administered 10 mg/kg enrofloxacin (ENRO) (group A) or 26.6 mg/kg flumequine (FLU) (group B) by gastric catheter daily for five consecutive days. A third group (n=6) was untreated controls. Eggs were collected from day one of treatment and up to 30 days after withdrawal of the drug. Egg white and yolk from each egg were separated, and ENRO, its metabolite ciprofloxacin (CIP) and FLU residues were analysed by a high-performance liquid chromatography method with fluorescence detection. The sum of ENRO and CIP was detectable in egg white on the first day of treatment in high-level concentrations (2007.7 μg/kg) and remained steady during administration. In egg yolk, residues were detectable at day one in lower concentrations (324.4 μg/kg), increasing to the end of treatment. After treatment, these residues decreased and were detectable up to day 8 in egg white, and day 10 in yolk. FLU residues during drug administration in white were detectable in high concentrations from day one to five (6788.4-6525.9 μg/kg), and in yolk, concentrations were lower during administration (629.6-853.9 μg/kg). After drug withdrawal, FLU residues remained longer in egg white (30 days) than in yolk (26 days). For both drugs, differences of concentrations between matrices were significant.     

Residue depletion of albendazole and its metabolites in aquacultured yellow perch (Perca flavescens)

Yu, D., Evans, E. R., Hasbrouck, N., Reimschuessel, R., Shaikh, B. Residue depletion of albendazole and its metabolites in aquacultured yellow perch (Perca flavescens). J. vet. Pharmacol. Therap.  35 , 560–562. Metabolism and residue depletion studies are conducted to determine the marker residue (MR) of a drug in a target tissue of food animals. The MR is used to monitor potential unauthorized use of drugs. The current work is a continuation of our efforts to study metabolism and depletion profiles of albendazole in multiple finfish species to determine a common MR. The results of this study suggest that albendazole sulfone metabolite could potentially serve as MR for albendazole in yellow perch muscle, similar to channel catfish and hybrid striped bass as reported previously by us.     

Residue depletion of melamine and cyanuric acid in catfish and rainbow trout following oral administration

Reimschuessel, R., Evans, E., Andersen, W. C., Turnipseed, S. B., Karbiwnyk, C. M., Mayer, T. D., Nochetto, C., Rummel, N. G., Gieseker, C. M. Residue depletion of melamine and cyanuric acid in catfish and rainbow trout following oral administration. J. vet. Pharmacol. Therap. 33 , 172–182. The intentional addition of triazines such as melamine to animal feeds and the lack of information about residue accumulation in food animals caused global concerns for food safety during 2007 and 2008. We report the results of a good laboratory practices (GLP) study to determine melamine and cyanuric acid residues in catfish and trout filets harvested at 1, 3, 7, 14, 28, and 42 days after a single oral dose of 20 mg/kg body weight of melamine, cyanuric acid, or melamine and cyanuric acid together. Peak melamine concentrations were 12.73 mg/kg (ppm) in catfish (mean = 9.98), 12.26 mg/kg in trout (mean = 7.89) on day 1. Within 7 days (catfish) or 14 days (trout) residues were <2.5 mg/kg, a level in foods accepted by many risk assessors worldwide to be unlikely to pose health risks to consumers. Peak cyanuric acid residues also occurred on day 1, 0.68 mg/kg in catfish (mean = 0.46), 2.59 mg/kg in trout (mean = 0.86). Cyanuric acid muscle residues were <2.5 mg/kg by day 3. The half‐lives for melamine and cyanuric acid ranged between 1 and 4 days. Renal crystals formed in fish given both melamine and cyanuric acid, persisting for weeks after the single dose.     

HPLC法测定氨苄西林钠可溶性粉中氨苄西林的含量

采用HPLC法测定氨苄西林钠可溶性粉中氨苄西林的含量.色谱柱为WaterssphericalC18(3.9mm×150mm,5μm),流动相为水-乙腈-1mol/L磷酸二氢钾溶液-1mol/L醋酸溶液(909∶80∶10∶1,V/V),检测波长254nm,流速1.0mL/min,柱温30℃,保留时间约4.5min.氨苄西林在0.25～2.0mg/mL范围内具有良好的线性关系(r=0.9999),平均回收率99.6%,RSD为0.3%.     

Pharmacokinetics of ampicillin in pigs

Na-ampicillin was administered by the intravenous or intramuscular route to pigs. Blood concentrations during 4–6 h after administration and tissue distribution were measured. Pharmacokinetic parameters indicated a two-compartment open model. The biological half-life was found to be 60 min and four intramuscular injections per day of 10mg/kg B.W. of Na-ampicillin were required to maintain a minimum plasma concentration of 0.4 μg/ml. Higher levels were found in both the urinary and digestive tract.     

Comparative plasma ampicillin levels and bioavailability of five parenteral ampicillin formulations in ruminant calves

Summary

Plasma ampicillin concentrations were determined in an eight‐ways crossover trial involving six ruminant calves, which were treated intravenously (i.v.) with sodium ampicillin at 15.5 mg/kg and intramuscularly (i.m.) with five different ampicillin trihydrate or ampicillin anhydrate formulations at 7.7 mg/kg. The mean plasma concentration‐time curve (C_p)after intravenous ampicillin sodium administration was described biexponentially, as: C_p = 38.8 e ‐0.0268t + 0.45 e ‐0.0058t.

Intramuscular injection, into the lateral neck, of Ampikel‐20^® and Polyflex^® resulted in 100 per cent bioavailabilities within 12 h post injection (p.i.), but the biological half‐lives (t½>) were different, being 2.1 and 3.8 h, respectively. Ampikel‐20^® produced the hïghest peak plasma drug concentrations (mean C _max:4.8 μg ampicillin/ml). After intramuscular injection of Penbritin® the mean bioavailability for the first 12 h p.i. was 63 per cent, the mean t½>, was 5.9 h, and the mean C_max was 1.8 μg/ml. Treatment with Albipen^® and Duphacillin^® resulted in low plasma ampicillin levels, which were maintained for 3 to 6 days p.i., limited bioavailability during the first 12 h p.i., and a mean t½> of 22.2 and 11.9 h, respectively. Plasma concentrations of ampicillin from four hours onwards after i.m. and s.c. administration of Ampikel‐20^® at a dose level of 15.5 mg/ kg were similar.

The duration of potentially therapeutic plasma ampicillin concentrations after administration of each formulation is presented. Pre‐slaughter withdrawal times for diseased calves are suggested for the different formulations studied.     

Enhancement of ampicillin bioavailability in pigs

Biliary excretion of Na-ampicillin was studied in 40–50 kg male castrated pigs fitted with a bile duct re-entrant cannula. There is a low recovery of antibiotic in the bile after an extraduodenal administration. The injection of sodium de-hydrocholate increased the bioavailability of ampicillin and decreased the volumes of distribution in the drug. The simultaneous administration of probenecid led also to an increased ampicillin bioavailability. The use of such regimes to obtain longer ampicillin dosage intervals is discussed.     

Pharmacokinetics and renal clearance of ampicillin in sheep

Pharmacokinetics and renal clearance of ampicillin were investigated in 13 sheep, following one single oral dose of 750 mg. A peak concentration in plasma 0.38 +/- 0.04 microgram/ml (mean +/- SEM) was achieved 95.3 +/- 5.95 min after drug administration. Absorption half-life was 44.4 +/- 4.4 min. The area under the plasma concentration curve was 94.6 +/- 4.5 micrograms.hour.ml-1, while in the case of urine it was 370.5 +/- 28.3 micrograms.hour.ml-1. Biological half-life of ampicillin was 110 +/- 3 min, with an elimination rate constant of 0.0064 +/- 0.0002 min-1. The values for volume of distribution and total body clearance were 8.2 +/- 0.71/kg or 52.0 +/- 4.2 ml/kg/min, respectively. The priming and maintenance doses, using MIC as 0.05 microgram/ml, were suggested to be 8.8 or 8.4 mg/kg, respectively, at an 8-h interval. For MIC of 0.5 microgram/ml, this dose should be 10 times higher. Renal clearance of ampicillin seemed to involve active tubular secretion. Renal excretion indicated either extensive metabolism or excretion through routes other than kidneys.     

蛋中的兽药残留

关注食品安全,倡导绿色消费逐渐成为人们追逐的主流。文章论述了兽药在蛋黄、蛋白中的沉积情况及其影响因素。内容新颖,可读性强,相信拜读后准会品出点“药”味。