20.500.12556/DKUM-77027 Kontrolirano sproščanje febuksostata in določitev koncentracije v serumu in urinu diplomsko delo univerzitetnega študijskega programa I. stopnje Controlled release of febuxostat and determination of serum and urine concentrations 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. 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. febuksostat kontrolirano raztapljanje stresni testi HPTLC LC-MS/MS Febuxostat controlled dissolution stress testing HPTLC LC-MS/MS true true false [M. Kouter] Slovenski jezik Angleški jezik Diplomsko delo/naloga 2020-08-11 14:23:26 2020-10-08 12:32:00 2022-08-09 14:16:04 2020-10-11 03:11:33 2020 0 Maribor 0 Maribor IX, 29 str. 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 544.351-145.1(043.2) 31899139 URN:SI:UM:DK:SCJRHM9L UN_Kouter_Marjetka_2020.pdf UN_Kouter_Marjetka_2020.pdf 1 CE08BE3DC7048C778DF9D1B8E0F095DF 95756e0a9294f1f9c2afcb5523273b5a024c15cffda86b82d804d4f5ade41b1f d1ca83f4-7c11-11eb-bb7a-00155d0001ca 20.500.12556/dkum/e07a11a7-3bc4-4737-9ed5-d8102574405b https://dk.um.si/Dokument.php?lang=slv&id=145704 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0