Razvoj stabilitetno-indikativne UHPLC metode za određivanje farmaceutski aktivnog spoja i njegovih srodnih spojeva

master's thesis

• Title (english): Development of stability-indicating UHPLC method for the determination of active pharmaceutical ingredient and its related substances
• Author: Kristina Bukač
• Mentor: Sandra Babić (mentor)
• Committee member: Sandra Babić (predsjednik povjerenstva)
• Committee member: Šime Ukić (član povjerenstva)
• Committee member: Lidija Furač (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2019-11-29, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom radu opisan je razvoj metode za analizu farmaceutski aktivne tvari cediraniba, njegovih onečišćenja i razgradnih produkata. Razvijena je metoda tekućinske kromatografije ultravisoke djelotvornosti (UHPLC) s detektorom s nizom dioda (DAD) s C18 kromatografskom kolonom i gradijentnim eluiranjem. Optimalni eksperimentalni uvjeti analize određeni su primjenom računalnog programa Drylab: gradijentno eluiranje u trajanju od 15 minuta, temperatura kolone 60 °C i pH-vrijednost pokretne faze 5,8. Provedena je prisilna razgradnja cediraniba u lužnatom i kiselom mediju, te pomoću okidativnog sredstva. Za analizu cediraniba i razgradnih produkata korištena je metoda UHPLC i metoda dvodimenzionalne UHPLC, obje vezane sa spektrometrijom masa visoke razlučivosti (spektrometar masa koji mjeri vrijeme preleta, QTOF). Na temelju dobivenih spektara mase i točnih masa određenih pomoću QTOF-a, pretpostavljene su strukture razgradnih produkata i način fragmentacije.

Abstract (english)

This work describes the development of an analytical method for the determination of active pharmaceutical ingredient cediranib, its impurities and degradation products using ultra-high performance liquid chromatography (UHPLC) with diode-array detector (DAD), C18 stationary phase and gradient elution. Optimal experimental conditions were determined by using computer software DryLab®: gradient elution with a run time of 15 minutes, column temperature 60 °C and pH-value of mobile phase 5,8. Influence of pH and the presence of oxidants on the degradation of cediranib active substance was investigated. Cediranib and degradation impurities were identified using ultra-high performance liquid chromatography and two-dimensional liquid chromatography coupled to high resolution mass spectrometry (quadrupole time of flight mass spectrometer, QTOF). The structures of degradation products were proposed based on mass spectra and exact masses determined by QTOF.

• Keywords: validacija; UHPLC; cediraniba
• Keywords (english): validation; UHPLC; cediraniba
• Language: croatian
• URN:NBN: urn:nbn:hr:149:624697
• Study programme: Title: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry; Course: Applied organic chemistry; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2022-01-01
• Created on: 2022-02-28 17:28:12