Razvoj nove elektroanalitičke metode za određivanje febuksostata

master's thesis

• Title (english): Development of novel electroanalytical method for determination of febuxostat
• Author: Ivona Milanović
• Mentor: Biljana Nigović (mentor)
• Committee member: Biljana Nigović (predsjednik povjerenstva)
• Committee member: Miranda Sertić (član povjerenstva)
• Committee member: Sandra Jurić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical analysis); Zagreb
• Defense date and country: 2017-05-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Febuksostat je snažan, nepurinski, selektivni inhibitor ksantin oksidaze koji se koristi u liječenju hiperuricemije te u pacijenata koji se liječe od leukemije, a u kojih postoji rizik od sindroma lize tumora.
U ovom radu istraživala se mogućnost primjene voltametrije u njegovoj analizi na dijamantnoj elektrodi s primjesama bora te optimizacija parametara cikličke i pravokutnovalne voltametrijske metode.
Febuksostat se ireverzibilno oksidira pri potencijalu od +1,35 V. Od ispitanih elektroda najboljom se pokazala BDD elektroda kojoj treba nakon svakog mjerenja polirati površinu kako bi se osigurala reproducibilnost rezultata. Prikladan osnovni elektrolit je Britton-Robinsov pufer pH vrijednosti 5. Struja vrha vala u cikličkoj voltametriji pokazuje linearnu ovisnost o drugom korijenu brzine promjene potencijala u rasponu od 25 do 2000 mV/s što ukazuje da se radi o difuzijski kontroliranom redoks procesu. U pravokutnovalnoj voltametriji optimalna vrijednost frekvencije iznosila je 300 Hz uz amplitudu pulsa 50 mV.
Nesteroidni protuupalni lijekovi, koji se često koriste kao terapija za smanjenje boli u ovih bolesnika, ne interferiraju s voltametrijskim isptivanjem febuksostata. Isto je pokazano i s nekim drugim analitima koji se mogu naći u njihovom serumu odnosno urinu bolesnika, a što su primjerice mokraćna kiselina, glukoza i dopamin. Dobra selektivnost pokazana je i analizom dozirnog oblika febuksostata jer nisu zamijećene interferencije pomoćnih tvari.

Abstract (english)

Febuxostat is a strong, non-purine, selective inhibitor of xanthin oxidase which is used in treatment of hyperuricemia and in patients who are receiving treatment for leukemia and are at risk of developing tumor lysis syndrome.
This research investigated possible application of voltammetric techniques in its analysis on boron-doped diamond electrode as well as optimization of parameters of cyclic and square-wave voltammetry.
Febuxostat oxidizes irreversibly at potential of +1,35 V. From all electrodes that were examined, the best proved to be BDD electrode whichs surface needs to be polished after each measurement to ensure the reproducibility of obtained results. The appropriate basic electrolyte is Britton-Robins buffer with pH value of 5. The wave peak current in cyclic voltammetry shows linear dependence to square root of potential change speed within range from 25 to 2000 mV/s, which suggests that redox-process is diffusion-controlled. In square-wave voltammetry the convenient frequency is 300 Hz with pulse amplitude of 50 mV.
Nonsteroidal anti-inflammatory drugs, which are often used as pain-reducing agents in these patients, do not interfere with voltammetric analysis of febuxostat. The same is demonstrated with some other analytes which can be found in their serum or urine, such as uric acid, glucose and dopamine. Good selectivity is proven with analysis of finished-dosage form of febuxostat since no interference of excipients was observed.

• Keywords: febuksostat; ciklička voltametrija; pravokutno-valna voltametrija; dijamantna elektroda s primjesama bora
• Keywords (english): febuxostat; cyclic voltammetry; square-wave voltammetry; boron-doped diamond electrode
• Language: croatian
• URN:NBN: urn:nbn:hr:163:905547
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-04-20 13:23:25