AEŠH metodes izstrāde radniecisku piemaisījumu noteikšanai Ivabradīna paraugos
Author
Sitčihins, Vladislavs
Co-author
Latvijas Universitāte. Ķīmijas fakultāte
Advisor
Nakurte, Ilva
Date
2017Metadata
Show full item recordAbstract
AEŠH metodes izstrde radniecisku piemaisjumu noteikšanai Ivabradna paraugos. Sitčihins V., zintniskais vadtjs Dr. m., Nakurte I. Maistra darbs, 50 lappuses, 35 attli, 12 tabulas, 15 literatras avoti, 2 pielikumi. Latviešu valod. Darba ietvaros analizts Ivabradns un 7 t zinmie radnieciskie piemaisjumi, izvlta savienojumu atdalšanas un detektšanas metode. Darba gait noteiktas katra individul savienojuma detektšanas robežas un linearittes apgabals. Prbaudta Ivabradna stabilitte stresa testšanas apstkļos, izmantojot masspektrometrisko (MS) detektšanu noteiktas dažu degradcijas produktu molekulro jonu m/z vrtbas. Divu hidrolzes produktu struktras ir identifictas, balstoties uz literatras datiem. Darba rezultt izstrdta AEŠH metode, kuru var izmantot tandm ar MS detektšanu. Metode ļauj selektvi noteikt hidrolzes, termolzes un sintzes blakusproduktu saturu Ivabradna paraugos. Prbaudja metodes atbilstbu EF jutbas, ticambas, atkrtojambas un robustuma prasībām validācijas testu ietvaros. Visi testi bija veikti saska ar ICH vadlnijm. Development of an HPLC Method for Estimation of Related Substances in Ivabradine. Sitcihins V., supervisor Dr. chem. Nakurte I. Master thesis, 50 pages, 35 figures, 12 charts, 15 literature references, 2 appendices. In Latvian. This thesis documents the development of an HPLC analytical method for detection of synthesis by-products and other related substances in Ivabradine. A sensitive detection method has been selected according to the analytes' structures and properties. Optimal chromatographic separation conditions have been experimentally determined. The thesis features a study of Ivabradine's stability and degradation. Basic and acidic hydrolysis, oxidation, thermolysis, as well as photolysis tests have been performed on Ivabradine. Mass spectra of some of the detected degradation products have been obtained. Two hydrolysis products have been identified, and their proposed structures have been found based on a scientific publication. MS-compatible HPLC analytical method has been developed for specific detection of 2 hydrolysis products, 2 thermolysis products and 7 known impurities in Ivabradine. The LOD's and the linearity ranges have been determined for each known substance. Tests of the method's compliance with the EP requirements of sensitivity, accuracy, repeatability and robustness have been executed. All the validation tests have been performed according to ICH guidelines.