Pharmacokinetics And Residue Depletion Of Cyadox In Carp

The pharmacokinetics and residue depletion of cyadox were studied in carp (Cyprinus carpio L.). Cyadox levels were determined in plasma after single intravenous (2 mg/kg bw) and oral (40 mg/kg bw) administration. The residue depletion levels of cyadox and its main metabolite (the 100 mg/kg feed additives level, the treatment period for 12w) in the several tissues were also observed in this paper. Plasma samples were collected from tail-vein at every different interval after two administration. Cyadox and desoxycyadox in the plasma was extracted and de-proteined by methanol. The contents were determined by reversed-phase high performance liquid chromatography (HPLC). The chromatography separation of the plasma samples were achievd on Hypersil-C18 column (5 μm, 150×4.6 mm) with Millemnium32 HPLC instrument using a degassed mixture methanol: water(15: 85/v: v) as the mobile phase, the flow-rate is 0.9 mL/min, the wavelength is 305 nm. The limit of detection(LOD) and the limit of quanthation(LOQ) of the cyadox and desoxycyadox standard solution is respectively 0.005μg/mL, 0.01 μg/mL and 0.01μg/mL. 0.02μg/mL. The standard calibration curve of drugs solution were linear in the range of 0.01-1.0ng/mL. The linear equation of cyadox and deosxycyadox were respectively C=6.0×10-6A-0.0019(r=0.9996) and C=11.78×10-6A+0.0119 (r=0.9989). When the plasma concentration of cyadox was at 0.015, 0.125. 1.0μg/mL, the intra-day and inter-day coefficient of variance was respectively less than 5% and 10%, the average recovery was over 85.9%. Whereas, the plasma concentration of desoxycyadox was at 0.03, 0.25. 2.0 μg/mL, the intra-day and niter-day coefficient of variance was respectively less than 10% and 15%, the average recovery was over 79.2%. The single dose intravemous and oral administrations concentration-time data were analyzed by pharmacokinetic compartment analysis soft (PKANALYST). The procession of cyadox after intravenous administration was fit the three-compartment open model pharmacokinetic equation:C=11.4201e-8.0650t+0.4926e-0.327t + 0.0736V0.0548t. The main pharmacokinetic parameters of cyadox in carp were as follows: AUC 3 .3503 μg h/mL, Vc 166.8574 mL/kg wb, CL 11.9393L/h,T1/2a. 0.086 h,T1/2beta 0.832 h.T1/2gamma, 12.64 h. The procession of cyadox after oral administration was fit the one-compartment open model, pharmacokinetic equaion:C=0.1371×(e-0.0823t-e-0.3099t). The main pharmacokinetic parameters of cyadox in carp were as follows: Cmax was 0.0623 ug/mL at 5.83 h post-injection. The Vj area was 7.2506 mL/kgbw.Moreover, according to the pharmacokinetics results, the feed additives was supplied and given the same diet supplemented with 100 mg kg-1 levels cyadox, the treatment period with feed additives 12 w consecutive days. Then, the tissue samples (muscle, skin and liver; 5 animals/time-point) were collected at every different interval (0, 2, 4, 5, 6, 8, 10, 15, 20, 25, 30 d) after administration. The samples were stored at-20℃ until analysis. When determination, the samples were dissolved under physical temperature and were used to analysis with two routes: one part-samples was treated with regular (method 1); other part-samples was dealed with hydrolysis (method 2). On the method 1, cyadox, desoxycyadox, QCA (floating) of the samples was detected simultaneously in one HPLC system. On the method 2, we considered the tissues occured to the bounding residue, therefore, the operation acted with hydrolysis method. By this method, the bounding and floating status of QCA were all released and detected as the final target metabolite. According to the condition, we can gain the drug withdrawal period. In method 1, the LOD and LOQ of cyadox, desoxycyadox, QCA (floating) were respectively 0.005, 0.01, 0.01μg/mL and 0.01, 0.02, 0.02μg/mL. The average recovery was over 69.2 ~ 86.3 % at the concentration lever of 0.02, 0.04, 0.08, 0.16 ug/mL and the intra-day and inter-day coefficient of variance were respectively less than 10 % and 15...