Pharmacokinetics And Tissue Residues Of Sanguinarine Metabolites In Broiler Chickens

Macleaya cordata contains a variety of active ingredients,mainly sanguinarine,chelerythrine,protopine,allocryptopine and so on.Macleaya cordata has been developed as China’s first two categories of veterinary drug Sangrovit because of growth and enhancing animal immune function.Although there are some pharmacokinetic studies of sanguinarine and chelerythrine in animals,there are few studies on pharmacokinetic studies in target animals.To study the pharmacokinetic study of sanguinarine and chelerythrine in broiler chickens,it not only provide the basis for clinical dose but also lay a forward-looking basis for the study of traditional Chinese veterinary medicine.1.Methodology:A rapid and reliable UPLC-MS/MS method was developed and validated for the sanguinarine,chelerythrine,protopine and allocryptopine in broiler plasma.Tetrahydropalmatine(TET)was chosen as the internal standard and plasma were separated by 10%trichloroacetic acid-acetonitrile(10:90,v:v).The assay quantifies a range from 0.78 ng·mL-1 to 100 ng·mL-1 for sanguinarine,chelerythrine,protopine and allocryptopine.The low limits of quantification were both 0.78 ng·mL-1.The relative recoveries of all analytes were from 97.4%to 110.4%.The accuracies and the precisions and stability of all analytes meet the requirements at the QC concentrations.The method had been successfully applied a content determination for plasma samples by long-term feeded the different concentrations of sangrovit.The result showed that it only had a concentration of 2.13 ± 0.78 ng·mL-1 for sanguinarine and the concentration of chelerythrine was not detected.It indicated that distribution and metabolism of sangrovit in the chicken body.2.A pharmacokinetic study:The blood was collected in wing vein at different time after oral administration for sangrovit or injection of the mixture for sanguinarine and chelerythrine.According to the measured concentration of blood the pharmacokinetic parameters were calculated.Results:the pharmacokinetic parameters for sanguinarine were that the Tmax was 0.9±0.652 h and the Cmax was 1.89±0.877 μg·L-1.The pharmacokinetic parameters of the injection group were that the t1/2 was 0.343±0.125 h and the CL was 6.800±0.630 L·(h·kg)-1.The bioavailability of hematoporphyridine was 17.42%.It showes that sanguinarine and chelerythrine were rapidly absorbed and rapidly distributed and rapidly metabolism but with low absorption,completely eliminated from plasma after 6 h.The concentration—time curve of sanguinarine by oral administration showed obvious multiple peaks suggesting the enterohepatic circulation of sanguinarine.