Simultana analiza fulvestranta i inhibitora o ciklinu D ovisnih kinaza micelarnom elektrokinetičkom kromatografijom

master's thesis

• Title (english): Simultaneous analysis of fulvestrant and cyclin D dependent kinases with micellar electrokinetic chromatography
• Author: Ivana Guštin
• Mentor: Miranda Sertić (mentor)
• Committee member: Miranda Sertić (predsjednik povjerenstva)
• Committee member: Biljana Nigović (član povjerenstva)
• Committee member: Tajana Silovski (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical analysis); Zagreb
• Defense date and country: 2022-07-22, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Rak dojke najčešće je sijelo raka među ženama. U z.adnjih desetak godina napravljena su opsežna klinička
istraživanja na temelju kojih su odobreni inhibitori o ciklinu D ovisnih kinaza. h1dicirani su za liječenje
lokalno uznapredovalog ili metastatskog raka dojke koji je HR+, HER2-, a koriste se, između ostalog, u
kombinaciji s fulvestrantom. Kako bi takva kombinacija bila što učinkovitija i sigurnija za pacijentice,
potrebno je razviti i jedinstvenu analitičku metodu kojom se može pouzdano odrediti njihova koncentracija
u krvi. Kapilarnoelektroforetske tehnike sve više nalaze primjenu u današnjici u području kontrole lijekova,
ali i detekcije lijekova u biološkom tkivu. Cilj ovog istraživanja bio je razviti novu kapilamoelektroforetsku
metodu kojom će se istovremeno moći detektirati i kvantificirati fulvestrant, palbociklib, ribociklib i
abemaciklib u krvi pacijenata u svrhu terapijskog praćenja lijekova te time i provesti odgovarajuću
individualizaciju terapije. Kao potencijalna metoda za njihovu analizu odabrana je micelama elektro kinetička
kromatografija.
Korištena je kapilara od izvučenog kvarca unutrašnjeg promjera 50 μm, ukupne duljine 40 cm, a uzorci su
injektirani u kapilaru tijekom 5 sekundi, pod tlakom od 50 mbar i pri temperaturi od 25 °C. Valna duljina na
kojoj su promatrani rezultati iznosila je 21 O nm. Kako bi nastale micele, dodan je surfaktant SDS u
koncentraciji od 60 mM. Od ostalih parametara, najbolja selektivnost i osjetljivost metode su utvrđeni
primjenom boratnog pufera u koncentraciji od 25 mM, dodatkom acetonitrila u pufer u udjelu od 1 O % te
primjenom napona od 28 kV.

Abstract (english)

Breast cancer is the most common type of cancer among women. Cyclin D dependent kinases inhibitors have
been approved based on extensive clinical trials that were carried out in the last ten years. They are indicated
in treatment for locally progressed or metastatic breast cancer, which is hormone positive, HER2 negative,
and are used, among other, in combination with fulvestrant. In order to secure that the following combination
is effective and safe for patients, it is necessary to develop a unique analytical method which can reliably
determine their blood concentration. Capillary electrophoresis techniques are becoming more and more used
in today's drug quality control, but also drug detection in biological tissue. The aim of this research was to
develop a new capillary electrophoresis technique which will be able to detect and quantify fulvestrant,
palbociclib, ribociclib and abemaciclib in blood samples of patients in the purpose of therapeutic drug
monitoring and in order to apply appropriate therapy individualisation. As a potential method for its analysis,
micellar electrokinetic chromatography has been chosen.
Capillary that was used is made of extracted quartz with an inner diameter of 50 m and total length 40 cm.
The samples were injected in the capillary for 5 seconds, under the pressure of 50 mbar and temperature of 25 degrees Celsius. The results were observed at the wavelength of 210 nm. In order to form the micelles, surfactant SDS
was added in the concentration of 60 mM. Beside surfactant concentration, other parameters that resulted
with the best selectivity and sensitivity are borate buffer in the concentration of 25 mM, addition of
acetonitrile to buffer in the fraction of 10 % and applied voltage of 28 kV.

• Keywords: fulvestrant; abemaciklib; palbociklib; ribociklib; rak dojke; kapilarna elektroforeza
• Keywords (english): fulvestrant; abemaciclib; palbociclib; ribociclib; breast cancer; capillary electrophoresis
• Language: croatian
• URN:NBN: urn:nbn:hr:163:140965
• 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; Embargo expiration date: 2024-07-24
• Created on: 2022-07-27 13:28:55