Prisilna razgradnja inkluzijskog kompleksa nabumetona i β-ciklodekstrina

master's thesis

• Title (english): Forced degradation study of nabumetone - β-cyclodextrin inclusion complex
• Author: Franjo Sakoman
• Mentor: Nives Galić (mentor)
• Committee member: Nives Galić (predsjednik povjerenstva)
• Committee member: Željka Soldin (član povjerenstva)
• Committee member: Đani Škalamera (član povjerenstva)
• Committee member: Ivan Nemet (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2023-02-21, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Nesteroidni protuupalni predlijek nabumeton se u jetri metabolizira u svoj farmakološki akivan
oblik, 6-metoksi-2-naftiloctenu kiselinu, koja djeluje kao selektivan inhibitor izoenzima
ciklooksigenaza-2. Prema biofarmaceutskom sustavu klasifikacije djelatnih tvari, nabumeton
pripada drugoj skupini koju karakteriziraju slaba topljivost i visoka permeabilnost. Njegova se
topljivost može poboljšati nastajanjem inkluzijskog kompleksa s cikličkim oligosaharidima,
ciklodekstrinima. Provođenjem studija prisilne razgradnje dobivaju se informacije o stabilnosti
lijeka i njegovim razgradnim produktima koji utječu na njegovu učinkovitost i sigurnost. U
sklopu ovog diplomskog rada korišten je spregnuti sustav tekućinske kromatografije
ultravisoke djelotvornosti i spektrometrije masa visokog razlučivanja za analizu razgradnih
produkata nabumetona nastalih u kiselom, lužnatom, i oksidirajućem mediju, pri sobnoj ili
povišenoj temperaturi, uz ili bez prisutnosti β-ciklodekstrina. Strukture i sheme fragmentiranja
razgradnih produkata nabumetona pretpostavljene su na temelju rezultata analize tandemnom
spektrometrijom masa.

Abstract (english)

Nonsteroidal anti-inflammatory prodrug nabumetone is metabolized in the liver into its
pharmacologically active metabolite, 6-methoxy-2-naphthylacetic acid, which acts as a
selective cyclooxygenase-2 inhibitor. According to the Biopharmaceutical Classification
System of drug substances, nabumetone is classified in the second group which is characterized
by low solubility and high permeability. Its solubility can be increased by the formation of
inclusion complexes with cyclic oligosaccharides cyclodextrins. Forced degradation studies
provide information about drug stability and its degradation products which affect its
effectiveness and safety. In this work, ultra performance liquid chromatography coupled with
high-resolution mass spectrometry was used for the analysis of nabumetone degradation
products formed in acidic, alkaline, and oxidizing media, at room or elevated temperature, with
or without the presence of β-cyclodextrin. Structures and fragmentation schemes of
nabumetone degradants were proposed according to the results of tandem mass spectrometry
analysis.

• Keywords: β-ciklodekstrin; inkluzijski kompleks; nabumeton; prisilna razgradnja
• Keywords (english): β-cyclodextrin; forced degradation; inclusion complex; nabumetone
• Language: croatian
• URN:NBN: urn:nbn:hr:217:250632
• 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: 2025-02-21
• Created on: 2023-03-01 10:12:08