Kontrolirano sproščanje febuksostata in določitev koncentracije v serumu in urinu

diplomsko delo univerzitetnega študijskega programa I. stopnje

Marjetka Kouter (Author), Petra Kotnik (Mentor), Maša Knez Hrnčič (Co-mentor)

Abstract

Febuksostat, zdravilo za zaviranje nastajanja sečne kisline, preprečuje napade putike. Protin, domače imenovan putika, je obolenje, ki predstavlja najpogostejši vnetni artitis pri moških, starejših od 40 let. V diplomskem delu smo v simulacijskih raztopinah (0,1 M HCl, fosfatni pufer s pH = 7,41 in deionizirana voda) kontrolno sproščali aktivno učinkovino febuksostat z metodo USP 1, ter določevali koncentracijo v različnih raztopinah, serumu in urinu. Za kvantifikacijo febuksostata sta bili uporabljeni občutlivi in specifični kromatografski metodi: tankoplastna kromatografija visoke ločljivosti (HPTLC) in tekočinska kromatografija z masno spektrometrijo (LC-MS/MS). Spreminjanju koncentracije febuksostata smo sledili z uporabo stresnih testov, staranja raztopin in kontroliranega raztapljanja v različnih simulacijskih raztopinah. Analizni metodi HPTLC in LC-MS/MS sta bili pripravljeni za določevanje koncentracije febuksostata v serumu in urinu. Najvišja vsebnost FEB po 24 h raztapljanja je bila zaznana v fosfatnem pufru. Z višanjem pH vrednosti topil smo ugotovili pozitiven vpliv na topnost FEB. S pomočjo stresnih testov smo določili degradacijo aktivne učinkovine. Najvišja degradacija se je pojavila pri uporabi 1M NaOH, kjer je po 48 h ostalo le še 0,03 % začetne mase FEB. Shranjevanje raztopin FEB pri višjih temperaturah povzroča staranje in posledično zmanjševanje koncentracije.

Keywords

febuksostat;kontrolirano raztapljanje;stresni testi;diplomske naloge;

Data

Language:	Slovenian
Year of publishing:	2020
Typology:	2.11 - Undergraduate Thesis
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[M. Kouter]
UDC:	544.351-145.1(043.2)
COBISS:	31899139
Views:	306
Downloads:	75
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary title:	Controlled release of febuxostat and determination of serum and urine concentrations
Secondary abstract:	Febuxostat, a drug for inhibiting uric acid production, prevents gout attacks. Gout is a common condition representing the most frequent inflammatory arthritis occurring in men aged over 40. In our study, active ingredient febuxostat was released by the USP 1 method in simulation solutions (0.1 M HCl, phosphate buffer with pH = 7.4 and deionised water), and the concentration in several solutions, serum and urine was determined. For febuxostat quantification were used two sensitive and specific chromatographic methods: high- performance thin-layer chromatography (HPTLC) and liquid chromatography-mass spectrometry (LC-MS/MS). Changes in febuxostat concentration were monitored using stress tests, stability tests, and controlled dissolution in various simulation solutions. HPTLC and LC-MS/MS analytical methods were prepared to determine concentration of FEB in serum and urine. The highest FEB content after 24 h of dissolution was detected in phosphate buffer. By increasing the pH of the solvents, we found a positive effect on the solubility of FEB. Degradation of the active ingredient was determined using stress tests. The highest degradation occurred with the use of 1M NaOH, where only 0.03 % of the initial mass remained after 48 h. Storage of FEB solutions at higher temperatures causes aging and reduction in concentration.
Secondary keywords:	Febuxostat;controlled dissolution;stress testing;HPTLC;LC-MS/MS;
Type (COBISS):	Bachelor thesis/paper
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages:	IX, 29 str.
ID:	11986276