Selektivnost elektroanalitičke metode za određivanje mesalazina i folne kiseline

master's thesis

• Title (english): Selectivity of electroanalytical method for determination of mesalazine and folic acid
• Author: Lucija Lacković
• Mentor: Biljana Nigović (mentor)
• Committee member: Biljana Nigović (predsjednik povjerenstva)
• Committee member: Sandra Jurić (član povjerenstva)
• Committee member: Ana Mornar Turk (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical analysis); Zagreb
• Defense date and country: 2020-06-23, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Folna kiselina pripada skupini B vitamina i važna je tijekom procesa rasta i diobe što se očituje u trudnoći gdje njezinim deficitom u trudnica koje spadaju u rizičnu skupinu može nastupiti spina bifida, odnosno defekt neuralne cijevi novorođenčeta. Važna je i za održavanje eritropoeze te ukoliko serumske razine padnu ispod 2 ng/mL nastupa megaloblastična anemija. Čest je deficit folne kiseline u osoba s upalnim bolestima crijeva.
Mesalazin pripada skupini protuupalnih lijekova – aminosalicilata. Razvijen je nakon spoznaje da je on aktivni dio lijeka sulfasalazina, koji sadrži i sulfapiridinski dio odgovoran za većinu nuspojava. Učinkovit je u blagim do umjerenim oblicima ulceroznog kolitisa, a koristi se i kod Crohnove bolesti iako je njegova učinkovitost u toj indikaciji upitna.
U ovom radu ispitana je selektivnost elektroanalitičke metode za istovremeno određivanje folne kiseline i mesalazina u Britton-Robinsonovom puferu pH vrijednosti 6, primjenom staklaste ugljikove elektrode modificirane nanošenjem 5 μL suspenzije ugljikovih nanocjevčica s vezanim aminoskupinama u 0,5%-tnoj otopini kitozana u 1%-tnoj octenoj kiselini pri frekvenciji 100 Hz, amplitudi pulsa 40 mV i porastu potencijala 10 mV.
Pravokutnovalni voltamogrami smjese mesalazina i folne kiseline ne pokazuju promjenu strujnih vrhova oksidacije mesalazina i folne kiseline nakon dodatka anorganskih soli (NaCl, KNO3, CaCl2 i NaHCO3) i glukoze. Interferencije s mesalazinom pokazuju askorbinska kiselina i mokraćna kiselina. Međutim, interferencije su uočene za koncentracije koje su više od onih endogeno očekivanih u biološkom uzorku.
Ispitan je utjecaj drugih aminosalicilatnih lijekova i metabolita mesalazina na oksidacijske vrhove folne kiseline i mesalazina. Sulfasalazin i balsalazid interferiraju s oba oksidacijska vrha, dok olsalazin interferira samo sa strujnim vrhom folne kiseline pa se može zaključiti kako bi novorazvijeni senzor bio prikladan za razvoj metode za simultano određivanje mesalazina i olsalazina. Metabolit mesalazina ne pokazuje interferencije u koncentracijama očekivanim u plazmi nakon biotransformacije pa ne bi utjecao na određivanje mesalazina i folne kiseline ovom metodom u biološkom uzorku.
Selektivnost metode na kraju je ispitana i na uzorcima tableta folne kiseline i mesalazina gdje nije pronađena interferencija pomoćnih tvari s oksidacijskim vrhovima niti prisutnost novih oksidacijskih vrhova koji potječu od pomoćnih tvari.

Abstract (english)

Folic acid belongs to the group of B vitamins and is important during the process of growth and division, which is manifested in pregnancy where its deficiency in pregnant women who belong to the risk group can occur spina bifida, or neural tube defect of the newborn. It is also important for the maintenance of erythropoiesis, and if serum levels falls below 2 ng/mL, megaloblastic anemia occurs. Folic acid deficiency is common in people with inflammatory bowel disease.
Mesalazine belongs to a group of anti-inflammatory drugs - aminosalicylates. It was developed after the realization that it is the active part of the drug sulfasalazine, which also contains the sulfapyridine part responsible for most side effects. It is effective in mild to moderate forms of ulcerative colitis, and is also used in Crohn's disease, although its effectiveness in this indication is questionable.
In this work, the selectivity of the electroanalytical method for simultaneous determination of folic acid and mesalazine in Britton-Robinson buffer pH 6 was investigated, using a glassy carbon electrode modified by applying a 5 μL suspension of carbon nanotubes with bounded amino groups in 0,5% chitosan solution in 1% acetic acid at a frequency of 100 Hz, a pulse amplitude of 40 mV and a potential increase of 10 mV.
Square-wave voltammograms of a mixture of mesalazine and folic acid do not show a change in the peak currents of oxidation of mesalazine and folic acid after the addition of inorganic salts (NaCl, KNO3, CaCl2 and NaHCO3) and glucose. Interference with mesalazine is shown by ascorbic acid and uric acid. However, interferences were observed for concentrations that were higher than those endogenously expected in the biological sample.
The effect of other aminosalicylate drugs and mesalazine metabolites on the oxidation peaks of folic acid and mesalazine was investigated. Sulfasalazine and balsalazide interfere with both oxidation peaks, while olsalazine interferes only with the folic acid current peak, so it can be concluded that the newly developed sensor would be suitable for developing a method for the simultaneous determination of mesalazine and olsalazine. The mesalazine metabolite does not show interferences in the concentrations expected in plasma after biotransformation, so it would not affect the determination of mesalazine and folic acid by this method in the biological sample.
Selectivity of the method was finally tested on samples of folic acid and mesalazine tablets where no interference of excipients with oxidation peaks nor the presence of new oxidation peaks derived from excipients was found.

• Keywords: folna kiselina; mesalazin; pravokutnovalna voltametrija; selektivnost metode
• Keywords (english): folic acid; mesalazine; square-wave voltammetry; selectivity of method
• Language: croatian
• URN:NBN: urn:nbn:hr:163:343961
• 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
• Created on: 2021-04-28 10:21:46