Quality Research On The API And Fomulation Screening Of AC4 Solution

AC4 was an ideal triazine anticoccidial drug,which was developed by Department of Pharmacology of Shanghai Veterinary Research Institute,Chinese Academy of Agricultural Science.This article was meant to develop a kind of HPLC method for the content determination of API and organic impurities of AC4;compeleted the detectation of inorganic impurities of AC4;created a GC-MS method for the detection and quantification of residual solvents of AC4;developed the fomulas of AC4 and a HPLC method for the content determination of its fomulas.The results were as follows:Estabilshed a HPLC method for the content determination of API and organic impurities of AC4 to control its quality rapidly and effectively.The results showed that the RSD of intra-day and inter-day precision were 0.27%and 0.73%;the RSD of accruration was 0.54%;the LOD and LOQ were 0.1 ng and 0.3 ng;the studied range was 20～200 μg/mL(R2=1);the content of each batch of AC4 was 95.39%～99.21%;the self contrast method of main component without correction factor was used to detect the organic impurities,and organic impurity whose content was more than 0.1%exsited and the total content of organic impurities were less than].0%.This method was simple,rapid and suitable for the content determination of API and organic impurities of AC4.According to reagents and chemicals used in the synthesis of AC4,the article completed the examination of inorganic impurities of AC4(batch:20130304,20130411,201304 17).The results showed that loss on dry was less than 1%;residue on ingnition was less than 0.1%;heavy metals were less than 10 ppm;chloride was less than 0.01%;ferric was less than 2 ppm;ammonium of AC4(batch:20130304)was less than 0.02%and ammoniums of AC4(batch:20130411 and 20140417)were less than 0.01%.A GC-MS method was developed and validated for the detection and quantification of residual solvents of AC4.The method was validated for methanol,ethanol and toluene.The results showed thatThe studied ranges of methanol,ethanol and toluene were 3 1.68～506.8,18.96～758.4,8.64～138.7 μg/m L(R2:0.995 8～0.997 1),the limit of quantification were 2.091,1.564,0.572 μg/kg,the RSD of precision were less than 5%,the average collection of preparation was in the range of 99.87%～100.39%.Ethanol was detected and its concentration was 0.184%～0.223%,which was less than 0.5%.A method obtained for the quantification of residual solvents in AC4 was simple and precise.Optimized the fomulas of AC4 solution by orthogonal test according to the average indication content,the formulas according to the result of this study were fomula 1(A3B2C2)and fomula 2(A1B2C2).Estabilshed a HPLC method for the content determination of fomulas of AC4 solution to control its content rapidly and simplely.The results showed that the maximum absorption wavelength of fomula 1 and 2 was 251 nm;the studied range was 5～200μg/mL(R2=1);the RSD of intra-day and inter-day precision of fomula were less than 2%;the average accruration and RSD of accurarion of fomula were 98.23%and 0.14%;after diluted I 000 times,the content of fomulas were stable.This method was simple,effective and suitable for the content determination of AC4 solution.