Karakterizacija inkluzijskih kompleksa cinarizina i odabranih ciklodekstrina spektrometrijom masa visokog razlučivanja

master's thesis

• Title (english): Characterization of inclusion complexes of cinnarizine with selected cyclodextrins by high-resolution mass spectrometry
• Author: Suzana Inkret
• Mentor: Nives Galić (mentor)
• Committee member: Nives Galić (predsjednik povjerenstva)
• Committee member: Željka Soldin (član povjerenstva)
• Committee member: Jasmina Rokov Plavec (član povjerenstva)
• Committee member: Iva Juranović Cindrić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2021-09-16, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Cinarizin je piperazinski derivat koji djeluje kao antihistaminik. Uglavnom se koristi za
liječenje posljedica Meniereove bolesti (endolimfatični hidrops) i nekih drugih poremećaja
vestibularnog sustava srednjeg uha, ali i za prevenciju i liječenje kinetoza. Budući da je slabo
topljiv u vodi, cinarizin se prema biofarmaceutskom sustavu klasifikacije djelatnih tvari
svrstava u lijekove skupine II. Već je ranije utvrđeno da se topljivost i bioraspoloživost
cinarzina moţe poboljšati kompleksiranjem s ciklodekstrinima, no inkluzijski kompleksi
cinarizina s ciklodekstrinima korištenjem spektrometrije masa do sada nisu proučavani. U
sklopu ovog diplomskog rada spektrometrijom masa je detaljno proučeno kompleksiranje
cinarizina prirodnim β-ciklodekstrinom kao i njegovim hidroksipropiliranim sintetskim
derivatom, 2-hidroksipropil-β-ciklodekstrinom. Stabilnost izoliranih odabranih iona
kompleksa cinarizina i ciklodekstrina u plinskoj fazi procijenjena je na temelju rezultata
eksperimenata tandemne spektrometrije masa koji su provedeni tehnikom kolizijom izazvane
disocijacije. Predložene su odgovarajuće sheme fragmentiranja te su konstruirani grafovi
ovisnosti relativne zastupljenosti iona kompleksa o primijenjenom kolizijskom potencijalu.

Abstract (english)

Cinnarizine is a piperazine derivative with antihistaminic properties. It is widely used for the
treatment of Meniere’s disease (endolymphatic hydrops) and a variety of other vestibular
disorders but for prevention and treatment of kinetosis as well. Due to its poor aqueous
solubility, cinnarizine is categorized as a class II compound according to the
Biopharmaceutical Classification System. Earlier studies have shown that its solubility and
bioavailability can be improved by complexation with cyclodextrins but inclusion complexes
of cinnarizine with cyclodextrins have not yet been characterized by mass spectrometry. The
complexation of cinnarizine by natural β-cyclodextrin and its hydroxypropylated derivative,
2-hydroxypropyl-β-cyclodextrin was extensively studied by mass spectrometry in this thesis.
The stability of selected complex ions in the gas phase was estimated by means of tandem
mass spectrometry analysis which was performed by collision-induced dissociation technique.
Corresponding fragmentation schemes were suggested and collision-energy breakdown
curves were constructed as well.

• Keywords: cinarizin; ciklodekstrini; inkluzijski kompleksi; spektrometrija masa
• Keywords (english): cinnarizine; cyclodextrins; inclusion complexes; mass spectrometry
• Language: croatian
• URN:NBN: urn:nbn:hr:217:535135
• 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: 2023-09-16
• Created on: 2021-09-21 07:57:21