Quality Control Study Of Aspirin Eugenol Ester

Aspirin Eugenol Ester（AEE）is a new chemical drug,an independently compound of aspirin and eugenol having antipyretic,analgesic and anti-inflammatory function,which was developed by Lanzhou institute of husbandry and pharmaceutical sciences of CAAS.Compared with aspirin and eugenol,AEE has advantages of low toxicity,reducing the stimulation and oxidation and avoiding gastrointestinal disease under the basis of not changing the aspirin and eugenol.To provide the safety in clinical trials,the quality control standard of AEE was mainly studied on this thesis.1.The aspirin eugenol ester content of reference substance was tested by using two kinds of fixed value methods of mass balance and nuclear magnetic resonance（NMR）.The reference substance content was tested by the methods of high phase liquid chromatography,drying loss and calcined residues,respectively and the results were taken into the mass balance method to calculate the reference substance content of AEE.The nuclear magnetic resonance method of determination of AEE content was built.The linearity,precision,repeatability and stability all accord with the requirements.The result of mass balance method was 99.82%and the NMR fixed value result was 99.53%.The results of determination are basically identical by mutual authentication of two methods.2.The different morphological crystal of AEE were prepared by recrystallization using ethanol,ethyl acetate and 95%ethanolas solvent,respectively.Scanning electron microscopy,X-ray powder diffraction,differential scanning calorimetry,thermogravimetric analyzer and infrared spectrum were used to analyse the sample.3.The residue solvent of acetone and ethanol in AEE was determined by headspace gas chromatography method using hydrogen flame ionization detector dimethyl sulfoxide as solvent and HP-INNOWAX as the analytical column.By the optimized conditions were that the equilibrium temperature is 80℃and balance time is 20 min.Experiment showed that the lowest detection limits of acetone and ethanol are 0.250μg/mL and 0.778μg/mL,and the average recovery were separately 99.20%and 100.52%.The highest residual of acetone and ethanol are 0.02%and 0.36%respectively.The analytical method is simple and available for determination of residual organic solvents in the raw material of aspirin eugenol ester having high accuracy and sensitivity,which could be.The method was applied to determine three batches of residual solvent residual in AEE,lining with the 2015 edition of Chinese pharmacopoeia about residual solvents limited.4.High performance liquid chromatography was adopted to constructrelated the content of salicylic acid,aspirin,eugenol in AEE using UV photometer as detector,C₁₈chromatographic column as separator,and mixture of acetonitrile and water（water:acetonitrile:ice acetic acid:tetrahydrofuran=70:20:5:5）as gradient elution.Methodology validation showed that the detection limits of salicylic acid,aspirin,eugenol are 0.034μg/mL,0.065μg/mL and 0.008μg/mL,respectively.The linear coefficients is greater than 0.99 and the average recovery is 98%¹01%.The methodis suitable for AEE quality control of salicylic acid,aspirin and eugenol with strong specificity,good precision,high accuracy and good linearity.The method is used to determine the content of three batches of AEE,and the total impurity is as high as 0.04%,according with limits stipulated in the 2015 edition of Chinese pharmacopoeia.