Prisilna razgradnja sofosbuvira i oseltamivira

master's thesis

• Title (english): Forced degradation of sofosbuvir and oseltamivir
• Author: Filip Tomić
• Mentor: Matija Cvetnić (mentor)
• Committee member: Matija Cvetnić (predsjednik povjerenstva)
• Committee member: Šime Ukić (član povjerenstva)
• Committee member: Dajana Kučić Grgić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2023-09-14, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Kroz posljednjih nekoliko desetljeća u području istraživanja i zaštite okoliša sve više pozornosti se pridaje takozvanim "novim onečišćujućim tvarima". Pojam "nove onečišćujuće tvari" obuhvaća sve one spojeve i tvari kojima se do nedavno nije pridavalo značenje kao ksenobioticima, a danas se sve više ispuštaju u okoliš u značajnijim količinama koje predstavljaju opasnost za okoliš. Jednu od najvažnijih skupina predstavljaju farmaceutici i sredstva za osobnu higijenu i njegu zbog toga što sadrže veliki broj različitih kemijskih spojeva koji imaju različit utjecaj na okoliš u koji se ispuštaju. U ovom radu ispitano je ponašanje i stabilnost dvaju farmaceutika, 0,1 mM otopina sofosbuvira i oseltamivira provođenjem testova prisilne razgradnje: a) lužnate hidrolize u prisutnosti 1,0 M otopine NaOH na sobnoj temperaturi tijekom 24 sata, b) kisele hidrolize u prisutnosti 1,0 M otopine HCl na sobnoj temperaturi tijekom 24 sata, c) oksidacije u prisutnosti 30%-tne otopine H2O2 pri sobnoj temperaturi tijekom 24 sata, d) termičke razgradnje (neutralne hidrolize) pri sobnoj temperaturi, 30 i 40 °C tijekom 168 sati (7 dana) i e) fotolitičke razgradnje djelovanjem UV svjetlosti jačine 600 W/m^2 pri 25 °C tijekom 6 sati. Analize svih izuzetih uzoraka provodile su se na HPLC-u gdje su za oba farmaceutika prethodno razvijene i validirane metode određivanja. Na temelju dobivenih rezultata validacije, obje metode zadovoljavaju zahtjeve prema svim parametrima: linearnost s koeficijentom determinacije većim od 0,99, točnost s vrijednostima analitičkog povrata između 70 i 130% te preciznost s RSD vrijednostima manjima od 10%. S obzirom na ispitivanja prisilne razgradnje može se zaključiti da su sofosbuvir i oseltamivir zadovoljavajuće i očekivane stabilnosti pri svim ispitanim uvjetima.

Abstract (english)

In recent decades, the so-called "new pollutants" have received increasing attention in the field of research and environmental protection. The term "new pollutants" includes all those compounds and substances that until recently were not considered xenobiotics and are now increasingly entering the environment in significant quantities and therefore posing a threat to the environment. One of the most important groups is pharmaceuticals and personal care products, as they contain a large number of different chemical compounds that have different effects on the environment into which they are released. In this work, the behavior and stability of two drugs, 0.1 mM solutions of sofosbuvir and oseltamivir, were tested by forced degradation tests: a) alkaline hydrolysis in the presence of a 1.0 M NaOH solution at room temperature for a period of 24 h, b) acid hydrolysis in the presence of a 1.0 M HCl solution at room temperature over a 24-hour period, c) oxidation in the presence of a 30% H2O2 solution at room temperature over a 24-hour period, d) thermal decomposition (neutral hydrolysis) at room temperature, 30 °C, and 40 °C over 168 hours (7 days), and e) photolytic decomposition exposed to UV light at 600 W/m^2 at 25°C over a 6-hour period. Analyses of all excluded samples were performed by HPLC, and the determination methods for both drugs were previously developed and validated. Based on the validation results obtained, both methods met the requirements for all parameters: Linearity with coefficient of determination higher than 0.99, Accuracy with analytical recoveries between 70 and 130%, and Precision with RSD values lower than 10%. Regarding the forced degradation tests, it can be concluded that sofosbuvir and oseltamivir showed satisfactory and expected stability under all tested conditions.

• Keywords: sofosbuvir; oseltamivir; prisilna razgradnja
• Keywords (english): sofosbuvir; oseltamivir; forced degradation
• Language: croatian
• URN:NBN: urn:nbn:hr:149:509600
• Study programme: Title: Chemical Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka kemijskog inženjerstva (magistar/magistra inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-01-01
• Created on: 2023-09-21 12:59:24