| AMO-COS suspension had been on market in overseas and it has not appeared in china. This study prepared AMO-COS suspension on basis of foreign prescription, studied pharmacokinetics and established methods for determination of residue in broilers.The AMO-COS suspension was development. AMO-COS suspension was made by suspending the AMO and COS in soybean oil. Including AMO 100 mg, COS 250000 IU, aluminum monostearate 20 mg, lecithin 0.5 mg, Span 80 3 mg, and VitE 25 mg per mL, dispersion 10 min at 10000 r/min, circulation 2 min in colloid mills.The colour of AMO-COS suspension is white. With the range of 2 to 200μg/mL, AMO has a good liner(r=0.999); with the range of 30 to 100μg/mL, COS has a good liner(r=0.998). The levels of AMO in three batches of pilots products were 99.29%, 98.76% and 99.23%. The levels of COS in three batches of pilots products were 98.41%, 99.60% and 97.65%. The mean recoveries of AMO at 2μg/mL, 25μg/mL and 200μg/mL three concentration levels were between 97.99～99.04% with RSD among 0.16～2.13%; the mean recoveries of COS at 30μg/mL, 60μg/mL and 200μg/mL three concentration levels were between 97.95~99.2% with RSD among 0.89～7.07%. After 12 months, the related substance in three batches of pilots products have changed to 1.7%1, 1.72% and 1.78%. The total decreased less than 5%. The experimental results indicated that the preparation was stable.Pharmacokinetics of AMO-COS suspension in broilers was studied. A HPLC detection method was developed to detect AMO and COS in plasma. The standard curves for AMO were liner in a range of 0.1~8μg/mL (r=0.999) and the standard curves for COS were liner in a range of 0.1~4μg/mL (r=0.998). The limit of detection of AMO and COS were 0.05μg/mL. The recoveries of AMO at 0.5μg/mL, 1.0μg/mL and 2.0μg/mL three concentration levels were between 85.13~98.36% with relative standard deviation (RSD) 2.01~6.55% and the recoveries of COS at 0.1μg/mL, 0.5μg/mL and 2.0μg/mL three concentration levels were 71.53~74.07% with relative standard deviation (RSD) 0.96~4.49%.24 broilers (2.5±0.5 kg) were randomly separated into 3 groups. Each group has 8 animals, intramuscular AMO suspension and COS aqueous solution and AMO-COS suspension respectively. The dosage was AMO 20mg/kg, COS 50000 IU/kg. Blood samples were collected up to 24 h respectively after administration and plasma concentration of AMO and COS were determined by a high performance liquid chromatography (HPLC). Pharmacokinetic analysis for AMO and COS were carried out by using DAS software with a two-compantmental mode. The main pharmacokinetic parameters for AMO suspension were as follows: Tmax, 0.97±0.08 h, Cmax, 3.73±0.97 mg/L; t1/2β, 7.46±2.97 h. The main pharmacokinetic parameters for COS aqueous solution were as follows: Tmax, 0.5 h; Cmax, 1.04±0.35 mg/L; t1/2β, 4.46±0.43 h. The main pharmacokinetic parameters for AMO-COS suspension were as follows: AMO: Tmax, 1 h;Cmax, 3.92±0.63 mg/L; t1/2β, 7.52±3.61 h; COS: Tmax, 1.06±0.18 h; Cmax, 1.23±0.12 mg/L; t1/2β, 6.63±2.28 h. The pharmacokinetics characteristics of single intramuscular adminstration of prepared AMO-COS suspension in this study indicated slow absorption,wide distribution and slower elimination than aqueous solution.The determination of residue method which determined AMO and COS concentration was studied. A HPLC detection method was developed to detect AMO and COS in liver, kindey, muscle and sebum cutaneum. The standard curves for AMO in four tissues were liner in a range of 0.025~0.8μg/g and the standard curves for COS in four tissues were liner in a range of 0.05~1.0μg/g. The detection of AMO and COS were 0.025μg/g and 0.05μg/g respectivly. The recoveries of AMO in four tissues were 68.22~81.79% with relative standard deviation (RSD) 1.3~4.73% and the recoveries of COS in four tissues were 76.96~100.73% with relative standard deviation (RSD) 1.41~7.09%. |
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