Isoniazid And Its Related Research

The main research in this dissertation is to analysis isoniazid and its related impurities. The species and contents of the impurities have been determined.Because there are significant defects in the methord of isoniazid content determination in Chinese Pharmacopoeia and European Pharmacopoeia,so we proposed the amending suggestions. There we have completed the major work to edit EDMF(European Drug Master File).First,the sample isoniazid spectroscopy characteristics were characterized by EA,MS,¹HNMR,¹³CNMR,FT-IR,DSC,UV,X-ray single crystal diffraction and so on.We identified the impurities which retention time was 2.07 min and 5.56 min in HPLC and their content was more than 0.1%.We got criterion impurities via chemical method.EA,MS,UV,FT-IR,NMR,DSC methods were used to confirm the structure of the impurities,and the result indicted that the peak which retention time was 2.07 min was produced by isonicotinic acid hydrazine salt,the retention time 5.56min was 2 5-di-(4-pyridyl) 1-H-1,3,4-triazole.In addition,we made a preliminary research about other impurities whose content were less than 0.1%.Second,a method of HPLC was developed to test isoniazid and its related impurities. The HPLC was carried out on stationary phase:Science home column(250*4.6 mm,5μm), and V_methanol:V_water=6:4(0.1%Docusate sodium) as diluents and mobile phase at a flow rate of 0.8 mL/min,temperature 25℃,and wavelength 263 nm with 20 ul injective volume.The result indicated that the HPLC method was simple and good repetition.Third,the quality standard was studied on the description,identification,and assay.An accurate and suitable HPLC method was established to determine the content and the related impurities.The HPLC method showed good linearity when it was evaluated respectively on isoniazid,isonicotinic acid hydrazine salt and 2,5-di-(4-pyridyl) -1,3,4-triazole,In this dissertation,according to the European Pharmacopoeia and the Chinese Pharmacopoeia the content of isoniazid was determined by KBrO₃ titration,the content detected was compared with that by HPLC method,the results indicated that there is significant defaults the isonicotinic acid hydrazine salt would influence the titration results, the HPLC method could avoid the testing error.The isoniazid drug stability study was performed under condition of ligh,heat,humidity,acid,alkaline,oxidation and accelerated stability also.The sample took place some degration under condition of light,hea,humidity experiments and the isonicotinic acid hydrazine salt content was different degree of dehydralation.The sample was unsteady under acidity,alkaline,oxidation conditions with some unknown other impurities.All this data offered the theory basis of control the production and store condition of the sample.