Optimizacija uvjeta fragmentacije deuteriranog letrozola i deuteriranog ribocikliba u trostrukom kvadrupolu spektrometra masa

master's thesis

• Title (english): Optimization of fragmentation conditions for deuterated letrozole and deuterated ribociclib in a triple quadrupole mass spectrometer
• Author: Ivor Babić
• Mentor: Miranda Sertić (mentor)
• Committee member: Miranda Sertić (predsjednik povjerenstva)
• Committee member: Lidija Bach-Rojecky (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: 2024-07-24, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Ribociklib je antineoplastik indiciran za liječenje postmenopauzalnih žena s lokalno uznapredovalim ili metastatskim
rakom dojke koji je HR pozitivan i HER2 negativan. Koristi se u kombinaciji s hormonskom terapijom koja smanjuje
učinak estrogena, a jedan od takvih lijekova je letrozol (inhibitor aromataze). Prilikom razvoja bioanalitičkih metoda
za terapijsko praćenje ovih lijekova ključna je uporaba unutarnjih standarda, koji eliminiraju pogreške nastale tijekom
pripreme uzorka za analizu. Optimalni unutarnji standard za tu svrhu jest izotopski označena verzija molekule koju
se želi kvantificirati, pri čemu se preferira upotreba deuterija zbog izobilja vodika u organskim molekulama. Glavni
cilj ovog istraživanja bio je optimizirati uvjete fragmentacije za deuterirani letrozol i deuterirani ribociklib koristeći
spektrometar masa s trostrukim kvadrupolom. Optimizacija je uključivala određivanje optimalnog fragmentorskog
napona, odabir fragmenata s najintenzivnijim signalom te određivanje optimalnih kolizijskih energija za generiranje
tih fragmenata. Pozitivna elektrosprej ionizacija deuteriranog letrozola formira molekulski ion s m/z 290,1. Optimalni
fragmentorski napon od 80 V daje najveći intenzitet signala tog molekulskog iona. Fragmenti m/z vrijednosti 194,2 i
221,0 najpogodniji su za analizu, s optimalnim kolizijskim energijama od 40 eV i 10 eV. Deuterirani ribociklib u
ionskom izvoru daje molekulski ion s m/z 441,2, pri čemu optimalni fragmentorski napon iznosi 160 V. Optimalni
fragmenti m/z 322,1, 252,2, 294,1 i 373,1 imaju najveći intenzitet signala pri kolizijskim energijama od 35 eV, 60
eV, 45 eV i 20 eV. Istraživanje je također pokazalo da je pozitivna elektrosprej ionizacija učinkovitija za analizu ovih
deuteriranih spojeva u usporedbi s negativnom elektrosprej ionizacijom jer generira fragmente s većim intenzitetom
signala.

Abstract (english)

Ribociclib is an antineoplastic indicated for treating postmenopausal women with locally advanced or metastatic breast cancer that is HR-positive and HER2-negative. It is used in combination with hormone therapy that reduces the effect of estrogen, one such drug being letrozole (an aromatase inhibitor). During the development of bioanalytical methods for
therapeutic monitoring of these drugs, the use of internal standards is crucial to eliminate errors arising during sample
preparation for analysis. The optimal internal standard for this purpose is an isotopically labeled version of the molecule
to be quantified, with deuterium being preferred due to the abundance of hydrogen in organic molecules.The main aim of
this research was to optimize fragmentation conditions for deuterated letrozole and deuterated ribociclib using a triple
quadrupole mass spectrometer. Optimization involved determining the optimal fragmentor voltage, selecting the
fragments with the most intense signal, and determining the optimal collision energies to generate these fragments.
Positive electrospray ionization of deuterated letrozole forms a molecular ion with m/z 290.1. An optimal fragmentor
voltage of 80 V gives the highest signal intensity for this molecular ion. Fragments with m/z values of 194.2 and 221.0 are
most suitable for analysis, with optimal collision energies of 40 eV and 10 eV. Deuterated ribociclib in the ion source
gives a molecular ion with m/z 441.2, with an optimal fragmentor voltage of 160 V. Optimal fragments with m/z 322.1,
252.2, 294.1, and 373.1 have the highest signal intensity at collision energies of 35 eV, 60 eV, 45 eV, and 20 eV. The
research also showed that positive electrospray ionization is more effective for analyzing these deuterated compounds
compared to negative electrospray ionization, as it generates fragments with more intense signals.

• Keywords: letrozol; ribociklib; deuterirani standard; spektrometrija masa; elektrosprej ionizacija
• Keywords (english): letrozole; ribociclib; deuterated standard; mass spectrometry; electrospray ionization
• Language: croatian
• URN:NBN: urn:nbn:hr:163:921646
• Study programme: Title: Pharmacy - integrated undergraduate and graduate - university study; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: sveučilišni magistar farmacije (sveučilišni magistar farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2026-07-24
• Created on: 2024-10-09 13:18:42