Study On The Quality Analysis Methods Of Dierucoyl Phosphatidylcholine

Dierucoyl phosphatidylcholine is one of the synthetic phospholipids,which is an important medicinal supplement in bupivacaine liposome and propofol liposome,and it accounts for the highest proportion in the composition of the preparations.Synthetic phospholipids are phospholipids obtained by chemical modification or total synthesis.They are more stable than natural phospholipids and are the key accessories for the preparation of liposome preparations.With the help of cholesterol,different synthetic phospholipids can meet the requirements of different drug components and successfully prepare liposomes.The purity and impurity content of phospholipids are very important to the stability of Liposome preparations,as well as the efficacy and drug safety.However,dierucoyl phosphatidylcholinehas is currently not included in any databases.The systematic quality research on the synthesis phospholipids in China is still in a blank state.Based on this,the quality study of dierucoyl phosphatidylcholine was studied with reference to the Pharmacopoeia collection standard and various technical guidelines of the same kind of approved auxiliary materials.Then the quality standard of dierucoyl phosphatidylcholine was established.The main elements of the work were as follows:Firstly,the characters ofdierucoyl phosphatidylcholine were investigated through the appearance,moisture absorption tests and solubility tests.The chemical structure was confirmed by ultraviolet spectrum,infrared spectrum,nuclear magnetic resonance spectrum and mass spectrometry.Secondly,according to the structural characteristics and synthesis process characteristics of dierucoyl phosphatidylcholine,its raw material mustard acid contains potential trace amounts of other fatty acid impurities(such as oleic acid,etc).Such fatty acids can also participate in the process reaction of glycerol phosphate choline to produce the corresponding fatty acid phosohatidylcholine,which is an analogue of phosphatidylcholine dismustard acid and was difficult to distinguish in thin layer chromatography.Therefore,the investigation of the purity of fatty acids(C22:1)was established.The acid was hydrolyzed from the product molecule and esterified.After the organic phase extraction,the direct sample test by gas chromatography was established,and the methodological research verification were conducted.This detection project can be applied to the quality study of similar synthetic phospholipids and can further improve the quality control of synthetic phospholipids.Thirdly,the main impurities of dierucoyl phosphatidylcholine have no absorbtion by ultraviolet characteristics.There are also difficult to control the impurities by high-performance liquid chromatography with general evaporation-light scattering detector(ELSD)because of its poor sensitivity and narrow linear range.Therefore,a thin layer chromatography method was established for the relevant material detection.This method sprayed by the copper phosphoric acid solution and the color was heated,then detected by the visible light.This test also conducted the methodological research verification tests.For solvent dichloromethane,tri-chloromethane and acetone used in the process,the residue of the solvent was detected and validated by means of a gas chromatographic top air sample method.The limits setting were referenced to the test data of multiple batches of products and the solvent safety limits listed in ICHQ3 C.The methodological research verification tests included specificity test,repeatability test,linearity range test and accuracy test,and the results of tests meted the requirements.Finally,according to the properties of this product,a method for determination of choline content of dierucoyl phosphatidylcholine was studied by means of high performance liquid chromatography with general evaporation-light scattering detector,and the method was verified,including specificity,linearity,precision and so on.According to the requirement of dierucoyl phosphatidylcholine as an injection accessory,a thermalizing substance inspection was added,that is,a method of endotoxins inspection was established and systematic methodological verification was conducted.This method can be used for rapid internal inspection of endotoxins in enterprises.