Study On The Related Substances And Quality Control Of Paroxetine Hydrochloride Tablets

Paroxetine hydrochloride is a new type of serotonin reuptake blocker(SSRI),which has antidepressant,anti-anxiety and other pharmacological effects in clinic,and has become one of the first choice for patients with depression.Because the imported paroxetine hydrochloride tablets imported from abroad are expensive and the process is tedious,according to the concept of "quality comes from design",domestic enterprises cooperate with our team to develop a new,simple and low-cost synthetic process.In order to ensure the safety of paroxetine hydrochloride generic drug products and improve product quality.This subject has conducted research on the substance,raw and auxiliary material compatibility and content determination of paroxetine hydrochloride generic drugs under the new process,in order to provide valuable reference for the quality control of paroxetine hydrochloride generic drugs produced by enterprises.The main research contents are as follows:The first part: The related substances of paroxetine hydrochloride tablets were studied by HPLC-DAD method.A method for HPLC analysis of related substances in paroxetine hydrochloride tablets was first established.UV detection wavelength,chromatographic column,mobile phase,column temperature,and dilution solvent were selected.Further detailed methodological studies on the applicability,specificity,linear range,quantification and detection limit,precision,accuracy,solution stability,durability of the established HPLC analysis method were performed.The results show that the method has the advantages of simple operation,strong specificity and high accuracy.The second part: The related substances of paroxetine hydrochloride produced by the new imitation process were investigated,the related substances above the impurity limit were determined,and the structure identification and source analysis were carried out.Through the establishment of a new preparation method-molecularly imprinted polymer method,the related substances in paroxetine hydrochloride were roughly separated by molecular imprinting polymer method,and then purified by semi-prepared liquid phase.The specific structure of the impurities was determined by LC-MS and NMR analysis.Through the study of the mechanism of impurity production,it is found that the four impurities are caused by the incomplete reaction between the starting material and the intermediate and the side reaction,so the production process can be improved to ensure the quality of the drug.This part mainly combines the molecular imprinting method and HPLC method to study the relevant substances in the sample,which improves the separation and enrichment efficiency of the relevant substances in the sample,and makes up for the lack of preparation of trace impurities in the drug.Fast impurity preparation.The third part: The compatibility test between paroxetine hydrochloride and excipients was established.The main purpose of this study is to determine whether the drug and excipients will increase the number of related substances in the drug or produce new related substances.The purpose of this study is to provide an effective reference for the study of follow-up tablets of paroxetine hydrochloride.The fourth part: The HPLC analysis method of paroxetine hydrochloride tablets was established,and the methodology was verified.The verification results show that the content detection method has strong specificity,high accuracy,stability and reliability,and is suitable for the quality control of the imitation tablet.