Establishment A Method For Analysis Of Anti-fibrosis Drug RY-17content And Related-substances And Its Application In Quality Research

RY-17 is an original small molecule candidate drug for anti-liver fibrosis designed and synthesized based on proline hydroxylase(P4H)inhibitors.This paper is divided into five chapters,the main content of the research is to establish the RY-17 content and related substances analysis method,for API synthesis monitoring,drug quality control,the basic physicochemical properties and stability research.The first chapter introduces the content and method of drug quality research.Drug quality research is one of the main contents of drug research and development.High performance liquid chromatography is often used in drug identification,content determination and related substances examination.RY-17 belongs to class 1 chemical new drugs,and its quality research has not been carried out before the study,so it is of great significance to establish the quality detection and analysis method of RY-17 and understand its physical and chemical properties.The second chapter mainly describes the establishment of liquid chromatograph analysis method of RY-17.Analytical Quality by Design(AQBD)principle is followed.Firstly,define the objective of the analytical method,and learn the key sample parameters(such as solubility,stability,etc.).Then,screen and adjust the key method parameters(such as mobile phase system,detection wavelength,p H,etc.),The key method attributes(resolution,number of chromatographic peaks,peak purity,etc.)were used as evaluation indexes.Finally,optimize the gradient program of the analysis method and thereby method was established.Three representative chromatographic analysis methods were established.Condition 1 was used to detect the key physicochemical properties and stability of RY-17.Condition 2 was systematic methodological verification and met the verification requirements;Condition 3 was used to support the impurity study.In the third chapter,the necessary methodological validation is carried out to ensure that the established analytical method is suitable for the corresponding detection requirements.According to the volume IV general principle 9101 analytical method verification guidelines of Chinese Pharmacopoeia(2020 Edition),the content and related-substances of chromatographic condition 2 about the specificity,linearity,precision,accuracy,etc.,were verified.The verification results meet the requirements,which ensure the reliability of this method of test results.In Chapter 4,in order to understand the key physicochemical properties and stability of the drug,the above chromatographic condition 1 was used to detect that API RY-17 was a low-solubility drug with good absorption in acidic parts of the body.According to researching the experimental method of influencing factors,the compatibility experiment of raw materials was designed.It was found that high temperature was the main degradation way of RY-17,and the main degradation product was impurity B.The talcum powder as an auxiliary material would reduce the stability of RY-17.In the study of crystal form,the crystal shape of RY-17 was characterized by X-ray powder diffractometer and other analytical instruments,and it was determined that RY-17 is a crystalline compound.The fifth chapter is the summary.In this paper,the development and verification of RY-17 content and related substance analysis methods were completed.By studying its key physicochemical properties and stability study,the quality study of the drug was further improved,Provided a basis for the selection of dosage forms and the development of formulation,as well as an experimental basis for the study of pharmacokinetics.