Preparation Optimization,quality Control Of Oxyclozanide Suspension And It’s Pharmacokinetics In Cattle

Oxyclozanide is a salicylanilide anthelmintic.Oxyclozanide mainly used for the treatment of fasciola hepaica,and have a effective killing effect on tapeworms and nematodes.The mechanism of action is mainly to inhibit the oxidative phosphorylation in the parasite,and prevent the production of ATP.In this paper,the preparation optimization,quality control and pharmacokinetics of Oxyclozanide Suspension were systematically studied.The following results were obtained.1、Prescription of oxyclozanide suspension was optimized.The prescription of oxyclozanide suspension was optimized with characters,sedimentation volume ratio and redispersibility as evaluating indexes by the single factor test and orthogonal test.The suspension（100 mL）was consisted of oxyclozanide（3.4 g）,Xanthan gum（2.5 g）,Magnesium aluminum silicate（0.7 g）,Sodium Pyrosulfite（0.5g）,Tween-80（3.0 mL）,and Sodium citrate（0.1 g）.2、The quality was studied to achieve quality control of oxyclozanide suspension.We made a preliminary study on character,identification,inspection,related substances and content determination of oxyclozanide suspension.Experimental results showed that:（1）oxyclozanide suspension was milky white suspension.（2）HPLC method was used to identify oxyclozanide suspension,where in the other components didn’t interfere in the HPLC identification,and the active ingredients are the same substances,so the HPLC method could be used for the identification.（3）The results of weight difference test,sedimentation volume ratio test and microbial limit test were proved to be qualified.（4）The HPLC methods was established for the determination of the content and related substances in the study.In the study of content,linear range oxyclozanide was 34.01μg/mL¹04.35μg/mL and average recovery rate was 100.1%.In the related substances study,The linear range of 2-amino-4,6-dichlorophenol hydrochloride and 3,5,6-trichlorosalicylic acid were 0.51²0.4μg/mL and average recovery rate were 99.9%and 98.6%respectively.The HPLC methods of content determination and related substances were accurate,reliable and easy to operate.3、The HPLC-MS/MS method was established for the determination of oxyclozanide in bovine plasma,and it’s pharmacokinetic was study.The concentration-time profile was well described by a one-compartment open pharmacokinetic model with first-order absorption.The peak concentration(C_max)of oxyclozanide was 15.870±2.855μg/mL.The time to peak concentration(T_max)was 22.032±3.343 h.The values for the Area under curve(AUC_（0-∞）)was 965.608±220.097μg/mL·h.The half life time of absorption(t_1/2α)was 14.706±2.509 h,and half life time of elimination(t_1/2β)was 14.938±2.650 h.The CL_F was 11.426±2.442 mL/h/Kg.These results showed that oxyclozanide suspension by oral administration was absorbed completely,and eliminated slowly.Oxyclozanide was principle in the plasma.In summary,We optimized the prescription of oxyclozanide suspension.The HPLC method was established to determine the content and related substances of oxyclozanide suspension.Futhermore,it’s pharmacokinetic of oxyclozanide suspension in cattle was studied.The above results provided a quality control standard for production,and corresponding basis for determining the reasonable dose,interval time of administration of the drug,and establishing a rational and effective dosage regimen for clinical.