Pharmacokinetics And Residues Of Albendazole In Eel (Monopterus Albus Zuieuw)

A HPLC method was developed for simultaneous determination of residues of ABZ, ABZSO,ABZSO₂ and ABZSO₂NH₂ in tissue of eel(Monopterus albus Zuieuw),and the pharmacokinetics and tissues residue depletion by this method in healthy eel.The pharmacokinetics and metabolism of Albendazole(ABZ) and its three principal metabolites(ABZ sulfoxide,ABZSO;ABZ sulfone,ABZSO₂;ABZ aminosulfone, ABZSO₂NH₂) were demonstrated following its oral administration in eel at 60±7g body weight as 15mg/kg dosage.The fish at 20â–¡water temperature was orally treated ABZ as a single dose,harvesting pharmacokinetic parameters,by using a software of 3P97 pharmacokinetic model to simulate the real situation of eel specimen.A reverse phase high performance liquid chromatogram(RP-HPLC) method was used to determinate the concentration of drug in plasma and muscle tissue with adhering skin by an ultraviolet (UV) detector at 292nm wavelength.A simple one-compartment open model best described albendazole and its metabolites in plasma.Extractions were by ethylacetate,the aqueous layer is evaporated to dryness.The residue is dissolved in mobile phase and defatted with N-hexane,and the aqueous layer is prepared for analysis by HPLC.The HPLC system used was the Varian series equipment, with a handmotion injection performed on a Microsorb-MV-C₁₈,5μm(250×4.6mm²) stainless steel column and a guard column(12.5×4.6mm²),which was programmed to inject a sample of 20μL.Detection of albendazole and its metabolites were performed on the variable wavelength detector at 292nm.The mobile phase consisted of MeOH-acetic acid buffer(0.01M)(10/90 v/v) solution(pH=3.8),and the flow rate was 1.5mL/min.The result showed that,calibration curves were linear for two analytes at 0.125～32μg/g of fortified.The recovery of ABZ and its three metabolites were 73%～96%.The detection limits for ABZ,ABZSO,ABZSO₂ and ABZSO₂NH₂ were 0.02μg/g,0.03μg/g,0.05μg/g and 0.05μg/g in plasma,respectively,were 0.01μg/g,0.01μg/g,0.03μg/g and 0.03μg/g in muscle,were 0.03μg/g,0.04μg/g,0.05μg/g and 0.05μg/g in liver,were 0.03μg/g,0.05μg/g, 0.04μg/g and 0.04μg/g in kidney.The variation coefficients for within 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 detect simultaneously albendazole and its three metabolites amine residues in eel.The plasma drug concentration-time data were fitted to use a single-compartment model.The absorption rate constant(K_α) of ABZ was found to be 0.24/h,whereas the elimination half-life(t_1/2ke) of the drug was 3.87 h.The area under the serum concentration-time curve(AUC) was 5.87μg/mL.h.The distribution volume(V_d/F) of ABZ was computed as 14.27 L/kg.The total clearance of ABZ(CL_b/F) was estimated to be 2.56 L/h·kg.The time-point of maximum plasma concentration of the drug(T_p) and the maximum plasma concentration(C_max) were calculated as 4.79 h and 0.45μg/mL.The absorption rate constant(K_α) of ABZSO was found to be 1.02/h,whereas the elimination half-life(t_1/2ke) of the drug was 11.45 h.The area under the serum concentration-time curve(AUC) was 39.75μg/mL·h.The distribution volume(V_d/F) of ABZ was computed as 5.40 L/kg.The total clearance of ABZ(CL_b/F) was estimated to be 0.33 L/h·kg.The time-point of maximum plasma concentration of the drug(T_p) and the maximum plasma concentration(C_max) were calculated as 5.03 h and 1.77μg/mL.Moreover,the metabolism of albendazole(ABZ) and its metabolites was studied in muscle tissue with adhering skin of eel.Eel were dosed once with 15mg/kg ABZ via a pliable stomach tube link with an injector.Muscle tissue samples were collected at 6,8, 12,16,24,36,48,72,96,120 and 144 hrs.ABZSO was present in high concentration at 2.46μg/g in eel muscle tissue with adhering skin following oral treatment at 8hrs.The study of pharmacokinetics at 20â–¡water temperatures revealed that the dose of 15mg/(kgbwd) after oral administration might be sufficient for the long-term maintenance of therapeutic concentration in the plasma of ABZ.Based on the results of the residue study,to ensure tissues samples are safe for consumption,it is suggested that the withdrawal periods should not be less than 21 days at 20â–¡.