Studies On Pharmacokinetics Of Florfenicol In Grass Carp(Ctenopharyngodon Idella)

Florfenicol (FF), a fluorinated derivative of thiamphenicol, is a syntheticchloramphenicol antibiotics for veterinary use in the latest generation. In this paper, amethod based on high-performance liquid chromatography (HPLC) was developed fordetecting florfenicol in plasma and tissues of grass carp (Ctenopharyngodon idella). Byusing this method, the pharmacokinetics and tissues residue depletion studies werecarried out in healthy grass carp after single dose oral and injection administration andmulti-dose oral administration.1. A method for determining florfenicol content in tissues of grass carp wasdeveloped based on the reversed phase high-performance liquid chromatography. In thismethod, acetone was used as extraction solvent, and the residue is defatted withn-hexane. The HPLC system used was the Island fluid chromatography (LC-20A)series equipment, detection of florfenicol was performed on the variable wavelengthdetector at225nm, the column temperature is30oC and and the flow rate was1.0mL/min. The mobile phase is acetonitrile-sodium phosphate buffer (30/70, V/V)solution. The results showed that the standard curves were linear for two analytes at0.025μg/mL~10.00μg/mL of florfenicol. The average recovery of florfenicol intissues was82.15±2.96%~93.59±1.53%. The detection limits for florfenicol were0.025μg/mL in plasma,0.015μg/g in muscle,0.025μg/g in liver, and0.050μg/g inkidney, respectively. Consequently, this method can be used to detect simultaneouslyflorfenicol residues in grass carp.2. Pharmacokinetics and tissue distribution of florfenicol in grass carp at25±1oCwere studied after they were given a single oral dose of l0mg/(kg.bw). The reslts showsthat plasma concentration-time curves were best described by a one-compartment modelwith1st order absorption, muscule concentration-time curves, kidneyconcentration-time curves and liver concentration-time curves were best described by atwo-compartment model with1st order absorption.The distribution volume (Vd/F) of FF was computed as2.379L/kg. In tissues, Time to maximum concentratiotn in the orderof magnitude were liver (1.336h)<kindey1.86h)<muscule (4.618h), shows thatflorfenicol was rapidly accumulated in kidney and liver.The dose of10mg/kg weight ofFF after IM injection, liver is peak time (Tp) for1.167h. After the injection ofFlorfenicol by single-dose with10mg/kg, the metabolism course of Florfenicol inplasma was accorded with two-compartment open model, and its theoreticalconcentration-time equation was as follows: C=10.909e-0.722t+2.004e-0.059t-12.913-1.426t.3. The tissue residue study was conducted after repeated oral administration atadosage of10mg/(kg.bw) for4day at25±1oC of water temperatures. For mostcountries, the rule for florfenicol residues is that the total concertration of florfenicol is lmg/kg. In this study, the total concertration of florfenicol in the muscle and skin at the1st day after the last administration was2.04μg/g, which was above1μg/g. At the3rdday after the last administration, the total concertration of florfenicol in the muscle andskin was0.25μg/g. The total concertration of florfenicol in the muscle and skin at the5th day after the last administration was0.075μg/g, which was lower than0.1μg/g ofthe maximum residue limit in Japan. No florfenicol could be detected after5day. Basedon the results of the residue study, to ensure tissues samples are safe for consumption. Itis suggested that the withdrawal periods should not be less than7days at25±1oC.