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doctoral thesis
Određivanje onečišćenja i razgradnih produkata ceritiniba
Zagreb: University of Zagreb, Faculty of Science, 2021. urn:nbn:hr:217:748219
Antolčić, Mia
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

Cite this document

Antolčić, M. (2021). Određivanje onečišćenja i razgradnih produkata ceritiniba (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:748219

Antolčić, Mia. "Određivanje onečišćenja i razgradnih produkata ceritiniba." Doctoral thesis, University of Zagreb, Faculty of Science, 2021. https://urn.nsk.hr/urn:nbn:hr:217:748219

Antolčić, Mia. "Određivanje onečišćenja i razgradnih produkata ceritiniba." Doctoral thesis, University of Zagreb, Faculty of Science, 2021. https://urn.nsk.hr/urn:nbn:hr:217:748219

Antolčić, M. (2021). 'Određivanje onečišćenja i razgradnih produkata ceritiniba', Doctoral thesis, University of Zagreb, Faculty of Science, accessed 20 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:748219

Antolčić M. Određivanje onečišćenja i razgradnih produkata ceritiniba [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Science; 2021 [cited 2024 November 20] Available at: https://urn.nsk.hr/urn:nbn:hr:217:748219

M. Antolčić, "Određivanje onečišćenja i razgradnih produkata ceritiniba", Doctoral thesis, University of Zagreb, Faculty of Science, Zagreb, 2021. Available at: https://urn.nsk.hr/urn:nbn:hr:217:748219

Metadata
TitleOdređivanje onečišćenja i razgradnih produkata ceritiniba
Title (english)Determination of ceritinib impurities and degradation products
AuthorMia Antolčić
MentorNives Galić (mentor)
Committee memberInes Primožič (predsjednik povjerenstva)
Committee memberŠime Ukić (član povjerenstva)
Committee memberIva Juranović Cindrić (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2021-06-11, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Universal decimal classification
(UDC)		54 - Chemistry. Crystallography. Mineralogy
Abstract
Ceritinib je djelatna tvar lijeka za terapiju bolesnika s metastaziranim karcinomom pluća nemalih stanica pozitivnih na kinazu anaplastičnog limfoma. Upotrebom tekućinske kromatografije visoke djelotvornosti spregnute s trostrukim kvadrupolnim analizatorom masa, razvijena je i validirana metoda za kvantitativno određivanje potencijalno genotoksičnih onečišćenja ceritiniba. Metoda je selektivna, specifična, linearna u rasponu od 1 μg L–1 (granica kvantifikacije) do 10 μg L–1, ponovljiva i robusna. Točnost metode potvrđena je određivanjem analitičkog povrata, čija je vrijednost bila u rasponu od 81,0 % do 107,3 %. Otopine uzoraka stabilne su minimalno 48 sati pri temperaturi od 4 °C. Također je razvijena metoda tekućinske kromatografije visoke djelotvornosti za analizu organskih onečišćenja ceritinib djelatne tvari, te je ista korištena za analizu nastalih razgradnih produkata ceritiniba. Razgradnja ceritiniba postignuta je pri povišenoj temperaturi, te u oksidacijskim, kiselim, i bazičnim uvjetima uz zagrijavanje. Predložene su strukture i pripadajući fragmenti 7 nastalih razgradnih produkata (RP1-RP7) korištenjem spektrometra masa visokog razlučivanja, Q-TOF.·
Abstract (english)
Ceritinib is an active pharmaceutical ingredient of a drug used for treatment of anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer. A method for quantitation of potentially genotoxic contaminants in ceritinib was developed and validated using ultra-high performance liquid chromatography coupled with mass detection with triple quadrupole analyzer. The developed method is selective, specific, linear from 1 μg L–1 (quantification limit) to 10 μg L–1, with adequate repeatability and robustness. Accuracy was determined by percentage recovery method, with obtained values between 81,0 % - 107,3 %. Sample solutions are stable for at least 48 hours when stored at 4 °C. A method for organic impurities determination in ceritinib was developed using Ultra-high performance liquid chromatography. This method was also used for separation of degradation products that were obtained using stress conditions (high temperature, oxidative, acidic, and basic environment). Structures of fragments and 7 new degradation products (RP1-RP7) were proposed using high resolution mass detection, Q-TOF.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:748219
Promotion2021
Study programmeTitle: Doctoral study in chemistry
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
Type of resourceText
Extent99 str. ; 30 cm
File originBorn digital
Access conditionsOpen access
Embargo expiration date: 2023-06-11
Terms of useLicence In copyright icon
Created on2021-06-24 11:54:59