Razvoj metode tekućinske kromatografije ultravisoke djelotvornosti za analizu razgradnih produkata lijeka dasatiniba

master's thesis

• Title (english): Development of ultra performance liquid chromatographic method for the analysis of dasatinib degradation products
• Author: Davor Šestan
• Mentor: Nives Galić (mentor)
• Committee member: Nives Galić (predsjednik povjerenstva)
• Committee member: Vesna Petrović Peroković (član povjerenstva)
• Committee member: Željka Soldin (član povjerenstva)
• Committee member: Predrag Novak (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2017-11-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom diplomskom radu razvijena je učinkovita i osjetljiva metoda tekućinske
kromatografije ultravisoke djelotvornosti (UHPLC) za analizu onečišćenja i razgradnih
produkta lijeka dasatiniba. DryLab je korišten za određivanje optimalnih uvjeta temperature,
vremena gradijentnog eluiranja i sastava pokretne faze kromatografskog odijeljivanja
metodom UHPLC. Najprikladnija kolona bila je Acquity UPLC CSH Phenyl-Hexyl 1,7 μm;
2,1 mm  100 mm. Optimalni uvjeti su: temperatura kolone = 50 °C, pH pokretne faze = 2
(fosfatni pufer za UHPLC, mravlja kiselina za LC-MS/MS analizu) i ukupno vrijeme trajanja
analize: 27,5 min.
Forsirana ragradnja dasatiniba provedena je u kiselom i lužnatom mediju, uz
prisutnost vodikovog peroksida te na povišenoj temperaturi. Za analizu razgradnih produkata
korišten je vezani sustav LC-MS/MS. Na temelju MS i MS/MS spektara pretpostavljene su
strukture razgradnih produkata i predložene odgovarajuće sheme fragmentiranja.

Abstract (english)

In this diploma thesis efficient ultra-high performance liquid chromatography
(UHPLC) method for determination of impurities and degradation product of dasatinib was
developed. DryLab software was used to determine the optimal conditions for UHPLC
separation like temperature, time of gradient elution and composition of the mobile phase.
The most efficient chromatographic column was Acquity UPLC CSH Phenyl-Hexyl 1,7 μm;
2,1 mm  100 mm. The optimal condition were: column temperature = 50 °C, pH of mobile
phase = 2 (phosphate buffer for UHPLC and formic acid for LC-MS/MS analysis), and total
time of analysis = 27.5 min.
Forced degradation of dasatinib was performed in acid and basic conditions, upon
addition of hydrogen peroxide, and on the elevated temperature. The LC-MS/MS system was
used for the analysis of the degradation products. Based on the MS and MS/MS spectra, the
stuctures of degradation products, as well as fragmentation shemes were proposed.

• Keywords: dasatinib; MS/MS; onečišćenja; forsirana razgradnja; UHPLC metoda
• Keywords (english): dasatinib; MS/MS; contaminants; degradation products; forced degradation; UHPLC method
• Language: croatian
• URN:NBN: urn:nbn:hr:217:128694
• 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: Open access; Embargo expiration date: 2019-12-01
• Created on: 2017-12-07 13:55:08