Study On Quality Standard Of Compound Rutin Tablets

Compound rutin tablets containing rutin and vitamin C two components.It is mainly used in the treatment of the fragile increase of blood capillary,and also for the treatment of hypertension,cerebral hemorrhage,retinal hemorrhage,hemorrhagic purpura,acute hemorrhagic nephritis,recurrent nasal hemorrhage,traumatic pulmonary hemorrhage,postpartum hemorrhage,etc.Original quality standards is the first volume of the chemical medicine and preparation of the Ministry of public health which rutin content determination by UV visible spectrophotometry,vitamin C content determination by iodine titration method.A large number of experimental data show that the content of the interference factors in the determination of the content of UV visible spectrophotometry is more than that of the special properties.A large number of experimental data show that interference factor is more if we determine content by ultraviolet visible spectrophotometry.Specificity is not strong also.The determination of the content of vitamin C by the method of iodine titration is not strong,and has many problems,such as high volatility,human factors and so on.In the other standard,there is a lack of uniformity and dissolution of the content,and the impurities are not controlled.These indicators can reflect the intrinsic quality of the drug.It is a subject about a comprehensive study of the quality standard of compound rutin tablets,and improved determination method.The rutin content was determined by the original UV visible spectrophotometry and the content of vitamin C in the determination of the iodine titration method improves for HPLC and pCEC.Rutin labeled amount is 20mg.According to the"Chinese Pharmacopoeia"?ChP?2010 edition of the two appendixes of the requirements,add the content uniformity of the inspection items.The long-term storage of rutin and vitamin C may be easily hydrolyzed and oxidized,so wo shoud make an detection of related substances.Through the detection of the impurity and structure analysis,analysis of the possible fragmentation pathway of impurities,we can effectively control the quality of compound rutin tablets.This thesis is divided into six chapters,the main contents include:The first chapter introduces the background and significance of the topic,the market usage of compound rutin tablet and the existing quality standards are reviewed.The research status and the significance of the determination of related substance and dissolution were introduced,and the characteristics and application of pressurized capillary electrochromatography were introduced.It aslo focuses on the significance of quality control of compound rutin tablets.The second chapter concerned with the method of determination for content and content uniformity of Vitamin C and rutin in compound rutin tablets by HPLC.The chromatographic analysis were carried out on a HALO⁵-C₁₈ column?250 mm×4.6 mm,5?m?with methanol-0.4%phosphate solution?60:40??adjust pH value to 3.0 with triethylamine?as mobile phase.The flow rate was 1.0 ml/min.The detection wavelength was 254 nm.The column temperature was 35?.The injection volume was 20?l.The linear range of rutin and Vitamin C were 5.0⁴0?g/ml?r=0.999?and 12.5¹00?g/ml?r=1.000?.The mean recoveries of rutin and Vitamin C were 99.7%with RSD=0.8%?n=9?and 97.9%with RSD=1.2%?n=9?.The content uniformity of rutin was conformed to quality standard.Verification by methodology,the method was simple,fast and accurate.It can be used to control the quality of Compound rutin tabletsThe third chapter concerned with the method of determination for related substances for compound rutin tablets by HPLC.The chromatographic analysis were carried out on a HALO⁵-C₁₈ column?250 mm×4.6 mm,5?m?with methanol-0.4%phosphate solution?45:55??adjust pH value to 3.0 with triethylamine?as mobile phase.The flow rate was1.0 ml/min.The detection wavelength was 362 nm.The column temperature was 35?.The injection volume was 20?l.The limits of detection?LOD,S/N=3?of quercetin and rutin were 0.010?g/ml and 0.015?g/ml.The limits of quantitation?LOQ,S/N=10?of quercetin and rutin were 0.04?g/ml and 0.05?g/ml.The linear range of quercetin and rutin were0.04¹2.0?g/ml?r=1.000?and 0.05³.0?g/ml?r=1.000?.The specificity and repeatability of the method were good.The method was simple,sensitive and accurate.By LC-MS/MS the structure of impurities was analyzed,and the possible cleavage pathway of the impurities was analyzed.The fourth chapter concerned with the method of dissolution for compound rutin tablets by HPLC,and the dissolution curve was drawed.The chromatographic analysis were carried out on a HALO⁵-C₁₈ column?250 mm×4.6 mm,5?m?with methanol-0.4%phosphate solution?60:40??adjust pH value to 3.0 with triethylamine?as mobile phase.The flow rate was 1.0 ml/min.The detection wavelength was 254 nm.The column temperature was 35?.The injection volume was 20?l.Intelligent drug dissolution apparatus for DT800 ERWEKA was usd,according to the"Chinese Pharmacopoeia"in2010 edition of two appendix dissolution determination first method?basket method?.Rutin dissolution medium was pH8.0 phosphate buffer.Vitamin C solution medium was0.1 mol/L hydrochloric acid solution.The dissolution time of rutin was 45 min.The dissolution time of Vitamin C was 30 min.The rotational speed was 100 r/min.Limit shall not be less than 80%of labelled amount.This method can be used for the determination of dissolution of compound rutin tablets.The fifth chapter concerned with the method of content determination for compound rutin tablets by pCEC.Trisep^TM-2100 pressurized capillary electrochromatography instrument was be used.The chromatographic analysis were carried out on a C₁₈ capillary column?300 mm×100?m i.d.,1.8?m,Suzhou universal chromatography Co.,Ltd.?with methanol-0.4%phosphate solution?adjust pH value to 3.0 with triethylamine?-acetonitrile?18:12:70?as mobile phase.The total flow rate was 0.05 ml/min.The detection wavelength was 254 nm.The linear range of rutin and Vitamin C were 2.0²0?g/ml?r=0.999?and 2.0²0?g/ml?r=0.999?.The mean recoveries of rutin and Vitamin C were 99.4%with RSD=1.2%?n=9?and 99.3%with RSD=1.4%?n=9?.Verification by methodology,the method was simple,fast and accurate.It can be used to control the quality of Compound rutin tablets.The method provides a new detection technology for the quality control of compound rutin tablets.The sixth chapter summarized the whole thesis and looked into the prospect of the further research work.