Studies On Pharmacokinetics And Residues Of Albendazole And Albendazole Sulphoxide In Carassius Auratus

A high performance liquid chromatography (HPLC) method was developed for determination of albendazole (ALB) and albendazole sulphoxide (ALB-SO) in the plasma and muscle of Carassius auratus. Plasma samples were extracted with ethyl acetate and detected with UV. Muscle samples were extracted with ethyl acetate, purified with n-hexane and detected with UV. The recoveries of ALB and ALB-SO ranged from 83.65%⁸6.92%, 82.93%⁹7.45% in plasma and 82.39%⁸5.82%, 84.60%⁹7.25% in muscle, respectively. The coefficients of variation of ALB and ALB-SO ranged from 3.40%³.70%, 4.16%⁴.53% in plasma and 2.59%⁵.26%, 2.46%⁴.36% in muscle, respectively. The limit of detection of ALB and ALB-SO were 0.05mg/L, 0.00625mg/L in plasma, and 0.05mg/kg, 0.00625mg/kg in muscle, respectively. The limit of quantitation of ALB and ALB-SO were 0.1mg/L, 0.0125mg/L in plasma, and 0.1mg/kg, 0.0125mg/kg in muscle, respectively.100 fish with body weights of 130 to 170g were randomly divided into 20groups for plasma pharmacokinetics and muscle residue elimination. The groups of plasma pharmacokinetics were treated orally via stomach tube at a single dose of 12mg/kg body weight and the plasma were collected at different intervals after administration of ALB; the groups of muscle residue elimination were treated orally via stomach tube at a dosage of 12mg/kg body weight per day for 5 days and the muscle were collected at different intervals after administration of ALB. The concentrations of ALB and ALB-SO in plasma and muscle were determined by reversed phase high performance liquid chromatography (RP-HPLC). The concentration-time date of ALB-SO in plasma and muscle were analysised with 3p97 computer program.The concentration-time data of ALB-SO in plasma after single oral adminstration in healthy Carassius auratus were fitted to a one-compartment open model with first-order absorption. The main pharmacokinetic parameters of ALB-SO in Carassius auratus were as follows: t_1/2(ka)10.91±1.33h, t_1/2(ke)11.95±1.24h, T_(peak)16.46±1.84h, Ka0.06±0.01h^-1, Ke0.06±0.01h^-1, C(max)0.28±0.07mg/L, AUC12.56±4.14mg/L·h. The results of the studies showed that ALB-SO was slowly absorpted and narrowly distributed at water temperature 15～18℃. The half-life and lag time were longer, and the concentration of ALB-SO in plasma was lower.The residue elimination showed that the ALB-SO concentrations in muscle were 0.787mg/kg on the 4th day, and fell to 0.064mg/kg on the 8th day. The ALB-SO concentrations in muscle fell below detection limit on the 24th day at water temperature (20±1)℃.