Razvoj kapilarnoelektroforetske metode za analizu ribocikliba

master's thesis

• Title (english): Development of cappilary electrophoretic method for analysis of ribociclib
• Author: Ivana Klarić
• Mentor: Miranda Sertić (mentor)
• Committee member: Miranda Sertić (predsjednik povjerenstva)
• Committee member: Daniela Amidžić Klarić (član povjerenstva)
• Committee member: Hrvoje Rimac (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical analysis); Zagreb
• Defense date and country: 2021-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Ribociklib je relativno novi antineoplatični lijek registriran 2017. godine koji se koristi u politerapiji u liječenju HR+/HER2- lokalno uznapredovalog ili metastatskog karcinoma dojke u kombinaciji s hormonskom terapijom, inhibitorom aromataze ili fulvestrantom.
Cilj ovog istraživanja bio je razviti novu, brzu, jednostavnu i ekološki prihvatljivu elektroforetsku metodu za analizu novog citostatika ribocikliba. S obzirom na bazični karakter ribocikliba, kao prikladna tehnika odabrana je zonska... More kapilarna elektroforeza uz dodatak unutarnjeg standarda diazepama. Analiza je provedena u kapilari efektivne duljine 30 cm, unutarnjeg promjera 50 μm, pri 20 °C.
Ispitan je SDS u kombinaciji s boratnim puferom (pH 9,18) i sa fosfatnim puferom (pH 2,5) te čisti fosfatni pufer. Uz boratni pufer bez dodatka SDS-a nije bilo moguće dobiti pik ribocikliba jer molekula ribocikliba pri takvom pH nije nabijena te je koeluirala s EOF. Smanjenjem koncentracije SDS-a u kombinaciji s fosfatnim puferom poboljšavao se oblik i simetrija pika. Optimalnim za analizu pokazao se fosfatni pufer pH 2,5 koncentracije 40 mM, bez dodatka SDS-a pri kojoj je postignuta najveća učinkovitost analize i dobivena najveća površina pikova, a postignuto zadovoljavajuće vrijeme analize i izbjegnuto Jouleovo zagrijavanje. Korištenjem napona 25 kV dobivena je dobra simetrija, površina i razlučivanje uz kratko vrijeme analize, a optimalnom temperaturom za analizu pokazala se temperatura od 20 ºC.
Kapilarna elektroforeza nova je analitička tehnika koja zbog mnogih prednosti (kratko vrijeme analize, mogućnost analize različitih vrsta analita, ekološka prihvatljivost, niski troškovi, jednostavnost i automatiziranost) ima veliki potencijal za primjenu u kliničkoj praksi te bi ju kao takvu metodu trebalo više koristiti kao alternativu ostalim skupljim i ekološki manje prihvatljivim analitičkim tehnikama. Less

Abstract (english)

Ribociclib is a relatively new antineoplastic drug that is used in polytherapy in the treatment of HR + / HER2- locally advanced or metastatic breast cancer in combination with hormone therapy, aromatase inhibitor or fulvestrant.
The main goal of this study was to develop a new, fast, simple, sensitive and ecologically acceptable electrophoretic method for the analysis of a new cytostatic drug ribociclib. Given the basic character of ribociclib, capillary zone electrophoresis has proven to be... More the most appropriate method. The analysis was carried out in a capillary with an effective length of 30 cm, an inner diameter of 50 μm, at 20 ° C.
In this study, different buffer combinations were tested: SDS in combination with borate buffer (pH 9.18), SDS with phosphate buffer (pH 2.5) and pure phosphate buffer. While using the pure phosphate buffer without addition of SDS, it was not possible to obtain a ribociclib peak because the ribociclib molecule was not charged at such pH and it eluted at the same time as EOF. Decreasing the SDS concentration in combination with phosphate buffer improved peak shape and symmetry. Phosphate buffer (pH 2.5) without addition of SDS, with a concentration of 40 mM has proven to be optimal for analysis, at which the highest analysis efficiency was achieved and the highest peak area was obtained, while satisfactory analysis time was achieved and Joule heating was avoided. Using a voltage of 25 kV, good symmetry, surface area and resolution were obtained with a short analysis time, and the optimal temperature for the analysis was 20 ºC.
Capillary electrophoresis is a new analytical technique which due to many advantages (short analysis time, possibility of analysis of different types of analytes, environmental acceptability, low costs, simplicity and automation) has great potential for application in clinical practice. Because of that, it should be used more in drug analysis, as an alternative to other, more expensive and less environmentally friendly analytical techniques. Less

• Keywords: ribociklib; kapilarna elektroforeza; kapilarna zonska elektroforeza
• Keywords (english): ribociclib; capillary electrophoresis; capillary zone electrophoresis
• Language: croatian
• URN:NBN: urn:nbn:hr:163:534077
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-07-15
• Created on: 2022-03-01 10:37:43