20.500.12556/DKUM-84021 Preučevanje fizikalno-kemijskih lastnosti nekaterih farmacevtskih učinkovin Study of the physicochemical properties of certain active pharmaceutical ingredients Aktivna farmacevtska učinkovina (API) je izraz, ki se uporablja za biološko aktivno sestavino zdravila. API v telesu povzročijo zahtevani učinek za zdravljenje določene bolezni. Stresno testiranje API lahko pomaga identificirati verjetne produkte razgradnje. S stresnim testiranjem lahko določimo tudi poti razgradnje in notranjo stabilnost molekule. Farmacevtske učinkovine lahko ločimo in jih razlikujemo od nečistot. Ugotavljanje stabilnosti je lahko sestavljeno iz kombinacije kromatografskega ločevanja in spektroskopskih tehnik. Za raziskovanje smo si izbrali tri farmacevtske učinkovine: fenofibrat, febuksostat in esomeprazol. Preverili smo njihovo stabilnost v raztopini metanola in jih izpostavili različnim stresnim pogojem ter prisilnemu staranju. Za kvantifikacijo smo uporabili tekočinsko kromatografijo z masno spektrometrijo (LC-MS/MS) in tankoplastno kromatografijo visoke ločljivosti (HPTLC). V raztopini metanola se je kot najbolj stabilen izkazal febuksostat. Koncentracija febuksostata je po 24 h ostala nespremenjena. S pomočjo stresnih testov smo določili razgradnjo posamezne farmacevtske učinkovine. Največji odstotek razgradnje je pri fenofibratu in febuksostatu povzročil dodatek 1 M NaOH. Po 48 h pri 60 °C je v vzorcu ostalo le še 2,36 % začetne mase fenofibrata. Pri enakih pogojih smo pri febuksostatu dosegli 83,09 % razgradnjo učinkovine. Do razgradnje esomeprazola je prišlo ob prisotnosti močne kisline in baze. Pri dodatku 1 M HCl je bila vsebnost esomeprazola po 24 h pri sobni temperaturi praktično nezaznavna. Shranjevanje vseh treh farmacevtskih učinkovin pri višjih temperaturah povzroča njihovo razgradnjo in posledično zmanjševanje koncentracije. Active pharmaceutical ingredient (API) is the term used for the biologically active component of a medicinal product. APIs produce the required effect in the body to treat a specific disease. Stress testing of APIs can help identify likely degradation products. Stress testing can also determine the degradation pathways and internal stability of a molecule. Active pharmaceutical ingredients can be separated and distinguished from impurities. Stability determination may consist of a combination of chromatographic separation and spectrometric techniques. Three active pharmaceutical ingredients were chosen for investigation: fenofibrate, febuxostat and esomeprazole. Their stability in methanol solution was tested and they were exposed to different stress conditions and forced ageing. Liquid chromatography-mass spectrometry (LC-MS/MS) and high-performance thin-layer chromatography (HPTLC) were used for quantification. In methanol solution, febuxostat proved to be the most stable. The concentration of febuxostat remained unchanged after 24 h. The degradation of each active pharmaceutical ingredient was determined by stress tests. The highest percentage of degradation for fenofibrate and febuxostat was caused by the addition of 1 M NaOH. After 48 h at 60 °C, only 2,36 % of the initial mass of fenofibrate remained in the sample. Under the same conditions, 83,09 % degradation of the active substance was obtained with febuxostat. The degradation of esomeprazole occurred in the presence of strong acid and base. After 24 h at room temperature, the addition of 1 M HCl made the esomeprazole content practically undetectable. Storage of all three active pharmaceutical ingredients at elevated temperatures causes their degradation and consequent decrease in concentration. fenofibrat febuksostat esomeprazol stresni testi HPTLC LC-MS/MS fenofibrate febuxostat esomeprazole stress testing HPTLC LC-MS/MS true true false [A. Garmut] Slovenski jezik Angleški jezik Magistrsko delo/naloga 2023-03-29 18:43:05 2023-05-05 08:54:01 2023-11-16 08:17:08 0000-00-00 00:00:00 2023 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.45:57.013(043.2) 152291331 MAG_Garmut_Ana_2023.pdf MAG_Garmut_Ana_2023.pdf 1 5E01190F996507FE9D04D6448B791ED6 986d3c12678db3b1884fdee852a2bfa8240d69e7c088d5d13d91a54ae1d29215 8621fca2-e386-11ed-8646-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=166997 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0