Разработка унифицированных методик в анализе некоторых антибиотиков, алкалоидов и витаминных препаратов

Аннотация

Subjects of the inquiry: medicinal preparations, substances and working standards of different firms-makers, countrics-produccrs — penicillin group, cephalosporins and their derivatives, antibiotics of aromatic series, pyridine alkaloids (tobacco), group of pyridine derivatives of synthetic origin, C group vitamins. Aim of the inquiry: development and improvement of physical and chemical methods for determination of some antibiotics, alkaloids and vitamins on physiologically active part of molecule. Method of the inquiry: physical and chemical investigations have been carried out with using IR- spectrophotometer UR-20; spectrometer Varian VXR-300; chromatograph “GC-17 A”, firm Shimadzu (Japan); chromatograph “Clarus-500”, firm Perkins Almar (USA); chromatograph “GH”, firm Agilent (USA); spectrophotometer CF-46 JIOMO; spectrophotometer CF-56, automatic monoradial, spectral diapason - 190-1100 nm; pH-metcr 150 m. The results achieved and their novelty: theoretical aspects of chcmism of reactions of the cyanic dyes formation with general conclusion of the given scientific materials concerning chromogenic reactions arc essentially enlarged. For the first time we examined chcmism of reaction of forming the cyanic dyes using it for identification of penicillin and cephalosporin antibiotics according to products of acidic hydrolysis and their further combination with glutaconic dialdchydc derivative. Practical application of reactions for identification of products of hydrolytic decay of P-lactamides in chromatographic research is considered. For the first time is suggested the technique for determination of sodium benzylpenicillin identity according to NMR- and PMR-spcctra which is confirmed by the most characteristic signals of the observed spectra; investigations by methods of NMR- and PMR-spectroscopy have been carried out to confirm products of reaction for formation of cyanic dyes and also identified the product of cyanic dyes of p-lactamidcs with PGA by IR-spcctroscopy. The techniques have been developed for determination of chemically important antibiotics of aromatic and heterocyclic series, vitamins of C- and PP-groups and pyridine alkaloids which arc presented mainly by tobacco alkaloids, based on using chromogenic reactions of cyanic and azomcthinc dyes formation. For the first time different ways have been developed for using physicochemical methods (GLS, spectrophotometry, based on the reaction of cyanic dyes formation) for determination of nicotine with the purpose of identification and assay of the main alkaloid content using inner standard (mcthylstcarat and tctracoscnc) being of interest for pharmaceutical analysis of pyridine alkaloids. The methods of discovering the metabolite sum by HPLC and SP analysis based on reaction of forming the cyanic dyes were elaborated, spectrophotometry is suggested to determine nicotine metabolites in biological liquids after repeated extraction with isolation of the substances of the main character (which were not undergone to oxidation on pyridine ring). The results of investigations concerning a combination of the products of ascorbic acid hydrolytic decomposition with primary amides and isonicotinic acid hydrazid arc summarized. Practical value: The results of our investigations allow to provide a scientific and methodological base for analysis of biologically active compounds used as medicinal agents, to develop techniques of their determination in accordance with physiologically active part of molecule and to improve a normative base on standardization of the identical medicinal substances. The main conclusions and theoretical materials of the thesis can be used while improving an educational process. Degree of embed and economic effectivity: the choice and unification based on physical and chemical methods, the most acceptable and reproduced under laboratory terms allow to determine possible and impossible directions for establishment of quality of important physiologically active medicinal agents. As a result of the performed investigations we can objectively approach to the questions of quality evaluation of antibiotics, alkaloids and vitamins with the aim of confirmation of structural fragments for organic compounds molecules, as well as for complete analysis of some objects of plant origin and to apply the developed techniques for appropriate biological liquids. Sphere of usage: in whole the thesis presents the developed scientific theoretical aspects of application of the reactions for formation of cyanic and azomcthinc dyes and practical results of investigations having definite achievements in the field of quality control of biologically active compounds used as drugs.