Validacija MEKC-MS/MS metode za kvantitativnu analizu anastrozola i letrozola u ljudskoj plazmi

master's thesis

• Title (english): Validation of the MEKC-MS/MS method for quantitative analysis of anastrozole and letrozole in human plasma
• Author: Lucija Ivec
• Mentor: Miranda Sertić (mentor)
• Committee member: Miranda Sertić (predsjednik povjerenstva)
• Committee member: Sandra Šupraha-Goreta (član povjerenstva)
• Committee member: Petra Turčić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical analysis); Zagreb
• Defense date and country: 2024-05-29, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Inhibitori aromataze anastrozol i letrozol koriste se u liječenju o estrogenu ovisnog i HER2
negativnog raka dojke kod postmenopauzalnih pacijentica, kao monoterapija ili u kombinaciji s
drugim lijekovima poput CDK4/6 inhibitora. Praćenje pridržavanja pacijentica ovako dugotrajnoj
terapiji ključno je za postizanje željenih ishoda liječenja.
Glavni cilj ovog diplomskog rada bio je validirati brzu i jednostavnu novorazvijenu MEKC-MS/MS
metodu za analizu inhibitora aromataze anastrozola i letrozola u biološkim uzorcima, što je važno
za terapijsko praćenje lijekova. Ispitivani validacijski parametri bili su linearnost i kalibracijska
krivulja, točnost i preciznost, stabilnost uzoraka u autosampleru te utjecaj matrice.
Validacija metode pokazala je da matrica ne predstavlja analitički problem prilikom ispitivanja
anastrozola (ME<1,3%) i letrozola (ME<17,3%). Parametar linearnosti ove analitičke metode
zadovoljen je za anastrozol (r>0,9945) u zadanom koncentracijskom rasponu od 20 do 200 ng/mL
kao i za letrozol (r>0,9802) u zadanom koncentracijskom rasponu od 30 do 300 ng/mL. Točnost i
preciznost (odstupanje, RSD<15%, odnosno <20% za LLOQ) zadovoljavajuće su za oba analita.
Također, stabilnost anastrozola i letrozola u autosampleru potvrđena je (odstupanje, RSD<15%), što
doprinosi pouzdanosti same metode.

Abstract (english)

Aromatase inhibitors anastrozole and letrozole are used in the treatment of estrogen-dependent and
HER2-negative breast cancer in postmenopausal patients, either as monotherapy or in combination
with other drugs such as CDK4/6 inhibitors. Monitoring patient adherence to such long-term therapy
is crucial for achieving desired treatment outcomes.
The main objective of this thesis was to validate a fast and simple newly developed MEKC-MS/MS
method for the analysis of aromatase inhibitors anastrozole and letrozole in biological samples,
which is important for therapeutic drug monitoring. The validation parameters tested included
linearity and calibration curve, accuracy and precision, sample stability in the autosampler, and
matrix effect.
The method validation demonstrated that the matrix does not pose an analytical problem for the
analysis of anastrozole (ME<1.3%) and letrozole (ME<17.3%). The linearity parameter of this
analytical method was met for anastrozole (r>0.9945) in the specified concentration range of 20 to
200 ng/mL, as well as for letrozole (r>0.9802) in the specified concentration range of 30 to 300
ng/mL. Accuracy and precision (bias, RSD<15%, and <20% for LLOQ) were satisfactory for both
analytes. Additionally, the stability of anastrozole and letrozole in the autosampler was confirmed
(bias, RSD<15%), contributing to the reliability of the method itself.

• Keywords: anastrozol; letrozol; rak dojke
• Keywords (english): anastrozole; letrozole; breast cancer
• Language: croatian
• URN:NBN: urn:nbn:hr:163:401606
• 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: 2026-05-29
• Created on: 2024-09-25 11:45:21