Quality Research Of Substance And Starting Materials Of Solifenacin Succinate

Solifenacin Succinate tablets is currently optimized drug for treating overactive bladder(OAB),which is widely used in clinical treatment and has a broad market prospect.The quality of the raw material drug plays a decisive role in the finished product.In order to ensure the safety and effectiveness of the drug prooduct,the experiment carrys on quality studys on the raw material and starting materials of solifenacin succinate,establishes analysis methods and verifies to eventally draw up the corresponding quality standard which looks forward to comprehensively analysize and control quality of raw materials of solifenacin succinate.The main contents of the subject research are as follows:1)Quality research of starting material 1(SM1)The experiment determined the impurity profile of SM1 according to the process synthesis route,then,developed the analysis method for the remaining impurities and verified the method.Finally,the method determined to use cyano column with pH7.4 buffer salt(0.02 mol/LNa2HPO4)-acetonitrile(65:35)as tmobile phase to flow in isocratic elution,the column temperature was 25℃and detection wavelength was 210 nm.The verification results show the specificity and accuracy of the method meet the requirements.The method can effectively and quickly detect related substances in SMI.The other inspection items conduct in accordance with the four General Principles of the Chinese Pharmacopoeia(2015 edition).2)Quality research of starting material 2(SM2)According to the process and structural characteristics of SM2,the experiment determined to study on(S)-isomer and impurity P containing chlorophenyl structural alerts.The chroma-tographic conditions were selected and optimized with reference to existing method and the national pharmacopoeias.For isomer impurity,the established pre-column derivatization-HPLC method can separate SM2 and isomers perfectly.For impurity P,the method simplifying on the basis of the related substance method of the finished product can effectively and quickly determine the impurity P in SM2.According to the ICH guidelines,the proposed impurity P limit is 0.015%.3)Quality research of solifenacin succinateFirstly,the experiment checked its appearance,identification and general inspection items with reference to the relevant testing methods of the Chinese Pharmacopoeia to determine the limits.Then,by studying the API synthesis route,the impurity transmission path in the process was analyzed to determine the impurity profile.Finally,the method of the related substances was developed,optimized and verified in combination with the existing methods.The results show that the established method has good specific,precision and high accuracy.Considering on this substance is a salt drug of organic bases,it is necessary to measure the acid radical content and base content of this substance at the same time,which can verify whether the acid radicals and bases are combined in a predetermined ratio and more comprehensively evaluate the quality of this substance.Therefore,this study established and verified the determination of the acid radical(succinic acid)of this substance.The results show that the method is accurate and reliable,which can be used for the determination of the succinic acid content of this substance.Impurity E(R-3-quinuclidinol)is a process impurity in the API synthesis process,controlled as a specific impurity in the European Pharmacopoeia.The experiment used TLC method to detect impurity E of this product because this impurity has no ultraviolet absorption.TLC conditions optimized on the impurity E detection method of the European Pharmacopoeia is highly sensitive and reproducible,which can be used to control the impurity E of this product.The study conducted a complete quality study on the two starting materials and the final drug substance of solifenacin succinate.The established analytical methods can accurately and effectively control the quality of various indicators to comprehensively valuate the quality of solifenacin succinate.Based on the results of quality research,the experiment established preliminary quality standards for the starting materials and API to provide a basis for formulation research and ensure the drug is safe,effective,and quality controllable.