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Pharmacokinetics And Residues Of Florfenicol In Crucian Carp (Carassius Auratus Gibelio)

Posted on:2008-01-04Degree:MasterType:Thesis
Country:ChinaCandidate:S Y ZhangFull Text:PDF
GTID:2143360218454873Subject:Aquaculture
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A HPLC method was developed for simultaneous determination of residues offlorfenicol and florfenicol amine in tissue of Crucian Carp (Carassius auratusgibelio),and the pharmacokinetics and tissues residue depletion by this method at 20℃water temperatures in healthy Crucian Carp.Extractions were ethyl acetate, the aqueous layer is evaporated to dryness. The residueis dissolved in mobile phase and defatted with hexane, and the aqueous layer is preparedfor analysis by LC. The HPLC system used was the Agilent 1100 series equipment, withan automatic injection performed on a Microsorb-MV-C18, 5μm (250×4.6mm2) stainlesssteel column and a guard column (12.5×4.6mm2), which was programmed to inject asample of 60μL. Thermostatted Column Compartment was used to maintain the columntemperature at 35℃. Detection of florfenicol was performed on the variable wavelengthdetector at 223nm. The mobile phase consisted of acetonitrile-acetic acid buffer (0.01M)(25/75 v/v) solution (pH=3.8), and the flow rate was 1.0mL/min. The result showed that,calibration curves were linear for two analytes at 0.25-32μg/g of fortified. The recoveryof florfenicol was 96-103% and the recovery of floffenicol amine was 94-104% in plasma,in muscle was 100-108% and 94-108%, in liver was 97-105%, in kidney was 97-108%and 96-109%, in skin was 97-108% and 97-110%. The detection limits for florfenicol andflorfenicol amine were 0.025μg/g and 0.010μg/g in plasma, respectively, were 0.010μg/gand 0.005μg/g in muscle, were 0.020μg/g and 0.010μg/g in liver, were 0.060μg/g and0.030μg/g in kidney, were 0.020μg/g and 0.010μg/g in skin. The variation coefficients forwithin a day and between days were less than 5% and 15%, respectively. In conclusion,this method is sensitive, accurate, comvenient and quick, which can be used to detectsimultaneously florfenicol and florfenicol amine residues in Crucian Carp.The plasma drug concentration-time data were fitted to use a single-compartmentmodel at 20℃. The absorption rate constant (Ka) of FF was found to be 0.75/h, whereasthe elimination half-life (t1/2ke) of the drug was 10.69 h. The area under the serumconcentration-time curve (AUC) was 53.74μg/mL·h. The distribution volume (Vd/F) ofFF was computed as 2.87 L/kg. The total clearance of FF (CLb) was estimated to be 0.19L/h·kg. The time-point of maximum plasma concentration of the drug (Tp) and themaximum plasma concentration (Cmax) were calculated as 3.59 h and 2.76μg/mL. Thetissue residue study was conducted after repeated oral administration at a dosage of 10mg/(kgbw). for 3 times. The results showed that the elimination half-life of flofenicolamine was longer than flofenicol. Florfenicol can be detected below 1μg/g in the muscleand skin in nature proportion in the 2nd day after the last administration, but can notdetected florfenicol at the 5th day. The average concentration of florfenicol amine wasdropped below 1μg/g in edible tissues at the 3rd day. It can be detected after 10th day, but can no longer be detected after 15 day. The total concertration of florfenicol andflorfenicol amine was above 1μg/g in the muscle and skin in nature proportion at the 3rdday after the last administration, and can be detected below 1μg/g at the 5th day.Florfenicol amine can still be detected at the 7th day, while florfenicol can no longer bedetected. Both of floffenicol and florfenicol amine can not be detected after 15 day.The study of pharmacokinetics at 20℃water temperatures revealed that the dose of10mg/(kgbw).d after oral administration might be sufficient for the long-termmaintenance of therapeutic concentration in the plasma of FE Based on the results of theresidue study, to ensure tissues samples are safe for consumption, it is suggested that thewithdrawal periods should not be less than 5 days at 20℃.
Keywords/Search Tags:RP-HPLC, Florfenicol, Carassius auratus gibelio, Pharmacokinetics, Residues, Withdrawal time
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