Pharmacokinetics And Tissue Residues Of Sanguinarine Metabolites In Broiler Chickens

Macleaya cordata?Willd.?R.Br.was already developed into a kind of feed additives in animal preparation which called Sangrovit.Sangrovit has been widely used for animal feed additive in China and European Union.Sangrovit is mainly contains aboudant sanguinarine?SA?and chelerythrine?CHE?.They can undergo reduction leading to the formation of noncharged dihydro metabolites.In order to provide a theoretical basis,technical support and clinical reference for the clinical application of the M.cordata extracts in the edible animals,this article is study on the pharmacokinetic and tissue residue study of the two alkaloids in broiler chickens.A sensitive and simple UPLC-MS/MS method has been developed and validated for the quantification of DHSA and DHCHE in plasma and muscle.The analytes were separated on an Agilent Poroshell 120 EC-C18 column using gradient elution.The determination was performed on a UPLC-MS/MS using multiple reactions monitoring mode under positive ionization mode.The quantitative ion transitions monitored were m/z 334.1?318.1 for DHSA and 350.1?334.1 for DHCHE.The assay exhibited good linearity?r?0.9978?for the two analytes over the calibration ranges from 0.2 to 200?g·L^-11 in plasma,the lower limit of quantification?LLOQ?is 0.2?g·L^-1 for both DHSA and DHCHE.In musle,the calibration ranges from 0.2 to 200?g·L^-1 for both DHSA and DHCHE,and LLOQ is 0.4?g·kg^-1 for both alkaloids.The method also showed satisfactory results in terms of specificity,accuracy and precision,recoveries,matrix effect and stability.The validated method was applied to the pharmacokinetic and tissue residue study of the two alkaloids in broiler chickens.The animals were orally administered Sangrovit solution at a dose of 20 mg·kg^-1 bw or intravenous administered mixed alkaloids(SA 0.03mg·kg^-1,CHE 0.015 mg·kg^-1),the blood was collected from the wing vein into heparinized centrifuge tubes at different time.Pharmacokinetic studies have shown that SA and CHE were quickly turned to DHSA and DHCHE,respectively.And then DHSA and DHCHE were rapidly absorbed but with low absorption,completely eliminated from plasma after 6 h.The concentration–time curve of DHSA in broiler chicken plasma showed obvious multiple peaks suggesting the enterohepatic circulation of DHSA.Broilers of age of 1 day were feeded for 42 days with Sangrovit,plasma and chest muscle was collected after fasting for 2 hours.The concentration of DHSA in plasma and muscle were 0.552?g·L^-1 and 0.804?g·kg^-1,respectively,only in 500 mg·kg^-1 group with Sangrovit.