Study On The Quality Standard Control And In Vivo Pharmacokinetic In Cattle Of Artemether Injection

This thesis conducted artemether is used in veterinary clinical cattle piroplasmosis studied at first.Paper has carried out the acute toxicity of artemether injection test;Determination of the Artemether in Artemether injection content with its stability test;pharmacokinetics of Artemether injection experiment in cattle.1.The acute toxicity test of Artemether injection was studied in rats and mice by intraperitoneal and oral medation respectively.Results show that the two ways are all LD50 > 5000 mg/kg.By the hematology detection,all of rats and mice whose take part in acute toxicity test,each indicators compared with the saline control group in the rats and mice no significant difference.Preliminary test results prove that the new artemether injection to the actual non-toxic,safe and reliable.2.To establish the HPLC method was developed for the determination of content of artemether injection method.Chromatographic conditions : Hypersil ODS?5 ?m,4.6 mm×150 mm?using C18 chromatographic column,column temperature 35 ?,injection volume 10 ?L,detection wavelength of 216 nm;Mobile phase of acetonitrile: water: tetrahydrofuran = 62:37:1?v/v?;Velocity,1.0 m L/min.Using the random chromatographic conditions for any of three groups of artemether injection content determination,the results of content determination for the labeled amount 96¹00%;Intra-day and inter-day precision is less than 3.0%,the average recovery was 97.51%.The results show that this method is accurate,reliable,high sensitivity,and have good reproducibility,the method operation is simple and efficient,can be used in the content determination of artemether injection.3.On the preparation of artemether injection stability test.Two factors affecting the heat and glare test and stability test during six months,the results are as flow: under the condition of high temperature 40 ?,artemether injection content dropped no more than 5%,in exposure to place way.In Glare test when the light intensity at 4500 Lx,the artemether content fell more than 5%,but less than 7%;Under the stability test artemether content were greater than 95%.Results show that artemether in transport,storage process should avoid light and avoid high temperature.4.Pharmacokinetic test in cattle of artemether injection,this research established a new method used high performance liquid chromatography-tandem mass spectrometry to determine the concentration of artemether injection by intramuscular and subcutaneous in cattle.The results showe that,in the intramuscular injection for cattle,the area under the curve: AUC?0-t?= 1133.83±44.83 ng·h·m L^-1;the maximal plasma concentration: Cmax = 151.06±6.99 ng·m L^-1;peak time Tmax=1.60±0.11 h;elimination half-life: T1/2???=13.62 h.In the subcutaneous injection for cattle thearea under the curve: AUC?0-t?=1134.84±143.81 ng·h·m L^-1;the maximal plasma concentration: Cmax = 80.27 ± 11.68 ng·m L^-1;the peak time Tmax = 3.89±0.18 h;Elimination of half-life : T1/2???=17.49 h.The data show that intramuscular injection and subcutaneous injection of artemether have a large AUC value,take intramuscular injection compared to subcutaneous injection of peak time faster,peak plasma concentration higher,and eliminate half-life Time is shorter.This study for application of artemether injection in animal piroplasmosis for laid a good foundation.