Studies On The Pharmacokinetics Of Furazofidone Metabolites (AOZ) In Eel (Anguilla Japonica) And The Preparation Of Standard Live Sample

1. The pharmacokinetics of furazofidone metabolites(AOZ)and the regulation of AOZ residue elimination in eel were studied by LC-MS/MS technology after the eel was soaked in drug. The results showed that the AOZ in muscle, plasma and liver could be detected after the eel was either soaked in 200μg/L of drug for 24 h or took orally for 0.5h, and it cost 24h to reach the peak of curve of metabolite concentration with the Cmax 31.35μg/kg, 98.29μg/L and 323.37μg/kg, respectively. Then the conc- entration began to fall, the metabolic rates tended towards flat in muscle and in plas- ma after treated for 84h, but in liver for 204h. The AOZ were still detected in plasma and in liver after 276h with the concentration of 4.56μg/kg, 11.71μg/L and 42.01μg/kg, respectively.2. The results showed that the concentration time curve of AOZ could be described by open three-compartment model after the data were analysed by DAS software. The main pharmacokinetics parameters in muscle, in plasma and in liver were as followed: the half-life of distribution (t1/2α) were 34.608 h, 26.257 h and 122.538 h, respectively; the half-life of elimination(t1/2β)were 292.143 h, 167.161 h and 122.544 h, respect- ively; the maximum concentration (Cmax)were 31.35 ug/kg, 98.29 ug/ L and 323.37 ug/kg, respectively; the maximum time (tmax ) were 24 h; the area under concentration -time curve (AUC 0-∞) were 4193.078 ug/L·h , 12015.91 ug/L·h and 27516.65 ug/L·h,respectively; the clearance (CL) in body were 0.048 L/h/kg, 0.017 L/h/kg and 0.007 L/h/kg, respectively.3. The method of standard sample preparation of AOZ in eel was also studied in this experiment by using the muscle as carrier through low temperature lyophilization. The adult eels weighed between 200g-300g were selected and soaked with 200μg/L of drug for 24 h. The live eels were killed after 300h and the head, the blood, the skin, the bone and the bowels were removed. And then the negative and the positive samp- les in a proportion of 1:4 were mixed and grinded fastly by a kitchen homogenizer (Moulinex, France). The grinded materials were added into hexane to delete fat and freeze-dried to powder by the freeze-drying instrument. Subsequently, the freeze -dried powder was vacuumed and sealed and sterilized by radiation .The results showed that the negative and the positive samples could be mixed homogeneously and the homogeneousness was perfect. The determination of the result showed that the residual concentration of AOZ in freeze-dried powder was 4.818μg/kg without the effect of radiation.