Optimizacija metode micelarne elektrokinetičke kromatografije spregnute s masenim spektrometrom trostrukog kvadrupola za razdjeljivanje šest lijekova za rak dojke

master's thesis

• Title (english): Optimization of a micellar electrokinetic chromatography method coupled to a triple quadrupole mass spectrometer for the separation of six breast cancer drugs
• Author: Katarina Sladonja
• Mentor: Miranda Sertić (mentor)
• Committee member: Miranda Sertić (predsjednik povjerenstva)
• Committee member: Biljana Nigović (član povjerenstva)
• Committee member: Jasna Jablan (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical analysis); Zagreb
• Defense date and country: 2023-06-26, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Rak dojke najčešća je zloćudna bolest kod žena. Da bi ishodi liječenja bili dobri važno je terapijsko
praćenje lijeka u plazmi. Time se sprječavaju nepotrebne nuspojave nastale previsokim dozama, ali
i poddoziranost zbog koje bolest nije liječena na adekvatan način te može napredovati. Metoda
MEKC-MS koja se u ovom radu koristila moćna je tehnika koja do sada nije opisana za analizu ovih
analita.
Cilj ovog rada je optimizirati parametre kapilarne elektroforeze i postići zadovoljavajuću separaciju
analita. Lijekovi koji su se analizirali su letrozol i anastrozol (inhibitori aromataza), fulvestrant
(antagonist estrogenskih receptora) te ribociklib, palbociklib i abemaciklib (inhibitori CDK 4 i 6).
Parametri koji su promatrani su temperatura, napon, koncentracija APFO-a, pH pufera, udio
metanola u puferu i mogućnost upotrebe drugih organskih otapala koja bi zamijenila metanol.
Zaključeno je da je separacija analita najbolja pri temperaturi od 30 °C, naponu od 25 kV,
koncentraciji APFO-a od 125 mM i pH pufera 10,5. Niti jedno organsko otapalo nije pokazalo bolje
rezultate od metanola, a analiza je najbolja pri udjelu metanola od 32% u puferu. Daljnjim
istraživanjima optimizirat će se parametri masene spektrometrije kako bi se razvila kompletna
MEKC-MS metoda za analizu.

Abstract (english)

Breast cancer is the most common cancer in women. In order for treatment outcomes to be good,
therapeutic monitoring of the drugs in plasma is important. This prevents unnecessary side effects
caused by excessive doses of drugs as well as underdosing which can lead to the progression of the
disease. MEKC-MS method used for this final thesis is a powerful technique that so far hasn’t been
described for this kind of analysis.
The aim of this thesis is to optimize the parameters of capillary electrophoresis for the separation of
analytes. The drugs that were analyzed were letrozole and anastrozole (inhibitors of aromatase),
fulvestrant (antagonist of estrogen receptors) and ribociclib, palbociclib and abemaciclib (inhibitors
of CDK 4 and 6). Parameters that were observed are temperature, voltage, concentration of APFO,
buffer pH, percentage of methanol in the buffer and the possibility of using other organic solvents
to replace methanol.
Best analyte separation was performed at a temperature of 30 °C, voltage of 25 kV, APFO
concentration of 125 mM and a buffer pH 10, 5. No organic solvent showed better results than
methanol. The analysis was best with a methanol percentage of 32 % in the buffer. Further research
will be aimed to optimize the parameters of mass spectrometry in order to develop a complete
MEKC-MS method for analysis.

• Keywords: rak dojke; micelarna elektrokinetička kromatofrafija; maseni spektrometar trostrukog kvadrupola
• Keywords (english): breast cancer; micellar electrokinetic chromatography; triple quadrupole mass spectrometer
• Language: croatian
• URN:NBN: urn:nbn:hr:163:234644
• 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: Embargoed access; Embargo expiration date: 2025-06-26
• Created on: 2024-01-04 15:46:15