Affirmation Of Rrapidil And Studies On The Quality Standard

Trapidil can inhibit selectivety cyclic nucleotide phosphodiesterase and inhibit growth factor of platelet. And trapidil also has the function of depressurization, anti-thrombus and so on. In clinic, trapidil can be used to prevent and cue angina pectoris, heart infarction, hypertension, cerebral thrombosis, sequelae of Cerebral vessels accident and so on.The establishment of a specific,simple and effective standard for qualify control is the basis for assuring quality of drugs.So it was importance for assuring product stability,safety and dfficiency to study it systematically and comprehensivly,to establish a good standard of Trapidil.Part 1 Affirm the structure of trapidilObjective:Affirm the structure of trapidil.Methods: compare the analysis of elemental analysis,UV, IR, MS, 1HN?MR,13C-NMR, CRS,DSC to determine the trapidil.Results:The CRS and substance of Trapidil have the same results of elemental analysis,UV, IR, MS, ¹H NMR,¹³C-NMR, CRS,DSC.Conclusion: The substance is completely trapidil. Part 2 Quality specification and technology study of TrapidilObjective: To provide basical datas for establishing standard for quality control,the studies of identification,exa-mination and assay have been carried out.Methods:1 Desciption: Trough the investigation of appearance , melting point, specific absorbance, the test methods are determined.2 Identification: 2.1Chemical method:Dissove about 0.1g in 3ml of water and 3ml of solution NaOH (0.4%),filt,then add one drop of copper sulfate TS;a blue precipitate is produced. 2.2TLC: developer: chloroform–methanol(95:5); detecting wavelength:254nm.3 Detection: 3.1Trough the investigation of acidity, clarify, chloride, ammonium,loss or drying,kesidue on ignition,the test methods are determined. 3.2Related Substances: use HPLC method. 3.3Organic volatile impurities: study chloroform, alcohol, acetoacetate by the GC method .4 Assay: Detemine the content by complexometry method.Results:1 Description: Colourless crystals or a micro-yellow crystalline or granular powder; odourless; Melting point: 100.5～103℃; specific absorbance: 850～900。2 Identification:â‘ Chemical method: a blue precipitate is produced.â‘¡TLC: developer: The principal spots can be seen at the same place.3 Detection: 3.1 The examination of acidity, clarify, chloride, ammonium, loss or drying, kesidue on ignition, accords with the specify. 3.2 Related Substances: 3.2.1 The system suitability: The column efficiency, calculated from Trapidil, is7000. 3.2.2 Detection wavelength: 292nm. 3.2.3 The system specificity: Under the condition of acid, alkali, oxidation, high temperature and illumination, the degradation products of Trapidil were well separated from each other. 3.2.4 The sensitivity test: The lowest detection limitation is 0.16ng. 3.2.5 The limit of Related Substances is not more than 1.0%. b Organic volatile impurities: The test results indicated that there are a little acetoacetate ( < 0.05%), and so the examination of acetoacetate is not tested.4 Assay: 4.1 The stability of solution:The sample was stable in 4 hours and the RSD was 0.1%. 4.2 Reproducibility test:The precision is good and the RSD was 0.1% and the result is 100.3%.Conclution: The methods of description, identity, related substances,assay for trapidil has been establishment of a specific,simple and effective standard for quality control.Part 3 Rontrolling parameter of Intermediateâ… ,â…¡Objective: To provide basical datas for establishing standard for quality control, the studies of identification, examination and assay have been carried out.Methods: 1 Desciption: Trough the investigation of appearance , melting point, the test methods are determined.2 Assay: The contents of intermediateâ… ,â…¡were measured by using HPLC method,column: Cl8; Mobile Phase:0.0lmol/l ammonium acetate(PH4.5)一methanol (80:20);detection wavelength:210nm,flowrate: 1.0ml/min.Results:1 Desciption:1.1 Colourless crystals or a micro-yellow crystalline or granular powder; Dissolve easily in methanol;Melting point:280～285℃. 1.2 Colourless crystals or a micro-yellow crys-talline or granular powder; Dissolve easily in methanol;Melt-ing point: 136～142℃.2 Assay:2.1 Intermediateâ… :The regression equation was:A=20885.9460C+8.3128,r=0.9999, the linear range was from 0.0525mg/m1to 0.4500mg/m1;The precision of method was goodand the RSD was 0.55%; The lowest detection limitation is 4ng.2.2 Intermediateâ…¡The regression equation was : A=39760.764C-89.7822,r=0.9999, r=0.9999,the linear range wasfrom 0.0430mg/m1to 0.4450mg/m1;The precision of methodwas good and the RSD was 0.55%; The lowestdetection limitation is 2ng.Conclution:The methods of description,identity,,assay of testing intermediateâ… ,â…¡has been established. This experiment provided reliable data for intermediateâ… ,â…¡quality control.