Razvoj i validacija nove bioanalitičke metode za istovremeno određivanje ribocikliba, letrozola i ibuprofena kapilarnom elektroforezom

master's thesis

• Title (english): Development and validation of a new bioanalytical method for simultaneous determination of ribociclib, letrozole and ibuprofen by capillary electrophoresis
• Author: Josipa Božić
• Mentor: Miranda Sertić (mentor)
• Committee member: Nives Galić (predsjednik povjerenstva)
• Committee member: Mirta Rubčić (član povjerenstva)
• Committee member: Morana Dulić (član povjerenstva)
• Committee member: Sanda Rončević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2023-02-17, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Rak dojke, s dominantnim podtipom HR+ HER2−, najčešći je rak u svijetu. Jedan od načina liječenja HR+ HER2− raka dojke je kombinacijom CDK4/6 inhibitora i inhibitora aromataze, često uz lijekove ribociklib i letrozol. Kapilarna elektroforeza metoda je koja se iz dana u dan sve više razvija te bi se s odgovarajućom reproducibilnošću i osjetljivošću mogla koristiti u svrhu terapijskog praćenja lijekova. U ovom je radu razvijena i validirana metoda za određivanje ribocikliba, letrozola i ibuprofena kapilarnom elektroforezom uz ketoprofen kao unutarnji standard. Separacija je postignuta uz 75 mmol dm−3 fosfat, 8,5 mmol dm−3 sulfobutileter-β-ciklodekstrin (SBE-β-CD) i 5 % izopropanola u radnom puferu pri naponu 15 kV i temperaturi 25 °C. Uzorak je injektiran hidrodinamički pri tlaku −50 mbar u trajanju 5 sekundi, nakon injektiranja ultračiste vode 6 sekundi. Metoda je precizna, linearna u rasponu masene koncentracije od 1 do 75 µg cm−3, specifična, robusna za promjenu temperature, koncentracije SBE-β-CD te napona.

Abstract (english)

Breast cancer is the most common type of cancer in the world, with subtype HR+ HER2− being most prevalent. HR+ HER2− breast cancer can be treated with hormone therapy, with ribociclib (CDK 4/6 inhibitor) and letrozole (aromatase inhibitor) being a commonly used medicine combination. Capillary electrophoresis is a rapidly developing method which could be used for therapeutic drug monitoring purposes after providing acceptable reproducibility and sensitivity. A method for analysis of ribociclib, letrozole and ibuprofen by capillary electrophoresis using ketoprofene as an internal standard was developed and validated. The separation was obtained with 75 mmol dm−3 phosphate, 8,5 mmol dm−3 sulphobutylether-β-cyclodextrin (SBE-β-CD) and 5% isopropanol. The hydrodynamic injection was performed at −50 mbar pressure for 5 seconds, after the injection of ultrapure water for 6 seconds. The method is precise, linear in a range of mass concentration of 1 to 75 µg cm−3, specific and robust for the change of temperature, SBE-β-CD concentration and voltage.

• Keywords: bioanalitika; kapilarna elektroforeza; letrozol; rak dojke; ribociklib
• Keywords (english): bioanalytics; breast cancer; capillary electrophoresis; letrozole; ribociclib
• Language: croatian
• URN:NBN: urn:nbn:hr:217:913389
• Project: Number: UIP-2019-04-8461; Title: Nova bioanalitička rješenja za personalizaciju terapije raka dojke; Title: Novel bioanalytical solutions in personalized breast cancer treatment; Acronym: OncoBioAnalytics; Leader: Miranda Sertić; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: UIP
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-02-17
• Created on: 2023-03-21 13:12:09