| Traditional Chinese medicine injections are a significant progress in the early medical industry in China.However,due to the relatively short history of development and the imperfect management in some aspects,the safety of traditional Chinese medicine injection has been questioned.In order to improve the safety and effectiveness,the state has carried out the reevaluation of traditional Chinese medicine injection.Zhengqingfengtongning injection is a kind of traditional Chinese medicine injection and the drug substance is sinomenine hydrochloride,which is extracted from the Chinese herbal medicine caulis sinomenii.Zhengqingfengtongning injection takes a good clinical effect on arthritis,rheumatoid arthritis and other diseases.For this injection,the research on related substances is not comprehensive enough.Based on this,the following studies were carried out on Zhengqingfengtongning injection in this paper.1.Determination of different sinomenine hydrochloride preparations using capillary electrophoresis method.A high-performance capillary electrophoresis(HPCE)method was established,and the content of sinomenine hydrochloride in sinomenine hydrochloride preparations was successfully determined within 4 minutes.which can acheive the rapid content determination of a large number of samples.The method is fast,efficient,green and environmentally friendly,which provides a valuable reference for further study on the quality of sinomenine hydrochloride preparations.2.Identification of impurities in sinomenine hydrochloride injection and analysis of quality control strategy.Established an ultra performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-QTOF/MS)method to detect the related substances in Zhengqingfengtongning injection.Six impurities were found in the injection,content determination results show that there are three kinds of compounds content has reached the identification limit.It was speculated that the three compounds were(9alpha,13 alpha,14alpha)-4-hydroxy-3,7-dimethoxy-17-methylmorphonan-6-one-8-sulfonic acid,sinoacutine and dinomenine,They are derived from API and preparation process.The impurities in Zhengqingfengtongning injection were analyzed comprehensively for the first time in this experiment,which provided a reference for the quality control of Zhengqingfengtongning injection.3.Determination of liquid liquid partition coefficient of sinomenine hydrochloride in different extractantsUsing ether,n-octanol,dichloromethane,ethyl acetate and trichloromethane as extractants,the distribution of sinomenine hydrochloride in different mixed solutions of organic and aqueous phases was compared by shaking flask method,and the effects of different temperatures(298.15 K,308.15 K,318.15 K)on the extraction ability of sinomenine hydrochloride from aqueous solution were investigated.The results showed that the distribution coefficients of sinomenine hydrochloride in the same mixed system were different at different temperatures,in addition to the organic phase of n-octanol,the distribution coefficients increased with the increase of temperature,other organic phases showed higher extraction ability at 298.15 K,which indicated that the temperature had an effect on the distribution coefficients of sinomenine hydrochloride in the mixed solutions of organic and aqueous phases.The experiment provides reference data for process modification.4.Solubility determination and equation fitting of sinomenine hydrochloride in ethanol water solutionIn this experiment,the equilibrium solubility of sinomenine hydrochloride in ethanol water mixed solvent at 283.15 K～ 308.15 K was determined by high performance liquid chromatography(HPLC).At the same time,the thermodynamic equations CNIBS/R-K equation and Van’t Hoff equation were introduced to fit the solubility data obtained in this experiment,and the relevant thermodynamic parameters were calculated.The results showed that the solubility of sinomenine hydrochloride in ethanol water mixed solvent was significantly higher than that in pure ethanol.With the increase of the mass fraction of ethanol in the mixed solvent,the solubility of sinomenine hydrochloride increased first and then decreased.When the ratio of alcohol to water was 5:5,the solubility of sinomenine hydrochloride reached the maximum.In addition,the experimental data showed that the solubility of sinomenine hydrochloride was affected by temperature.Within the experimental temperature range,the solubility increases with the increase of temperature.Thermodynamic equation fitting results show that the predicted values accord with the experimental data well,the thermodynamic parameters Δ H,Δ S and Δ G were all greater than 0,indicating that the dissolution process of sinomenine hydrochloride in ethanol water mixed solvent was nonspontaneous and endothermic.In this experiment,the thermodynamic equation obtained by fitting the solubility data provides reliable reference data for the recrystallization process in the production process of API. |
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