Razvoj metode zadoločevanje ß-blokerjev z GC-MS

magistrsko delo

Simon Madžarac (Avtor), Helena Prosen (Mentor), Franc Požgan (Član komisije za zagovor), Drago Kočar (Član komisije za zagovor)

Povzetek

β-blokerji so zdravilne učinkovine, ki se uporabljajo za zdravljenje srčne aritmije, srčnega popuščanja in v redkih primerih za zdravljenje hipertenzije. V magistrski nalogi je predstavljena metoda za določevanje β-blokerjev z GC-MS analizno tehniko. Priprava vzorca je potekala brez derivatizacije, z ekstrakcijo na trdno fazo in s primerjavo različnih ekstrakcijskih kolon. Za preliminarne analize sem pripravil raztopine ( = 50 mg/L učinkovine) tablet v acetonitrilu, ki so vsebovale enega od sledečih beta blokerjev: atenolol, bisoprolol, karvedilol, metoprolol in propranolol. Na podlagi preliminarnih analiz sem v nadaljevanju pripravil umeritvene krivulje z raztopljenimi standardi v acetonitrilu (bisoprolol, metoprolol in propranolol), v območju od 5 do 25 mg/L. Določeval sem jih kot osnovne spojine ali njihove adukte ter na dva načina snemanja (TIC ali SIM). Pri optimizaciji SPE ekstrakcije sem uporabljal različne kolone (LC-18, DSC-18, OASIS HLB, X-C in X-CW). Prav tako sem primerjal ekstrakcijo iste raztopine pod različnimi pogoji, s spremenjenim pH ali z dodajanjem NaCl. Ločeno sem pripravil umeritvene krivulje s standardi v urinskem ekstraktu, v enakem koncentracijskem območju. Pri pripravi treh končnih urinskih vzorcev (0,15; 0,2 in 0,4 mg/L) sem kot topilo uporabil urin. Tekom eksperimentalnega dela sem preveril še prebojni volumen SPE kolone, ponovljivost ekstrakcije in primerjal umeritvene krivulje standardov, raztopljenih v acetonitrilu ali v urinskem ekstraktu. S končno metodo sem lahko uspešno določil bisoprolol, metoprolol in propranolol s koncentracijo vsaj 0,2 mg/L, najvišje izkoristke ekstrakcije osnovnih raztopin (urin) pa sem izračunal pri določanju v TIC načinu snemanja, in sicer: (85,0 ± 2,4) % za metoprolol, za propranolol (90,1 ± 6,0) % in (59,4 ± 8,3) % za bisoprolol.

Ključne besede

beta blokerji;urinski vzorci;priprava vzorca;ekstrakcija na trdno fazo;SPE ekstrakcija;plinska kromatografija;masna spektrometrija;GC-MS;magistrska dela;

Podatki

Jezik:	Slovenski jezik
Leto izida:	2020
Tipologija:	2.09 - Magistrsko delo
Organizacija:	UL FKKT - Fakulteta za kemijo in kemijsko tehnologijo
Založnik:	[S. Madžarac]
UDK:	543.544.3:543.51(043.2)
COBISS:	15486979
Št. ogledov:	750
Št. prenosov:	232
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Angleški jezik
Sekundarni naslov:	Development of a GC-MS method for determination of β-blockers
Sekundarni povzetek:	β-blockers are active pharmaceutical compounds used for treating heart arrhythmia, as a precaution against heart failure, and as well for treating hypertension. As part of my master's degree thesis I developed a GC-MS method for determination of β-blockers. Sample preparation is based on solid-phase extraction without any derivatization needed. It includes a comparison of different solid-phase extraction cartridges. Solutions in concentration of 50 mg/L were used for preliminary analyses. Pharmaceutical tablets, containing different beta blockers (atenolol, bisoprolol, carvedilol, metoprolol, and propranolol), were dissolved in acetonitrile. Standard solutions in acetonitrile (bisoprolol, metoprolol and propranolol) for calibration curves (5–25 mg/L) were prepared from solid standards, based on the results of preliminary analyses. Analytes were determined either unchanged or as adducts, and mass spectrometry was used in both modes, using total ion current and selected-ion monitoring as well. During solid-phase extraciton method optimization, different cartridges were used (LC-18, DSC-18, OASIS HLB, X-C, and X-CW), also aqueous solutions of beta blockers with different pH or added NaCl, were used to compare the solid-phase extraction recovery. Method development began with standard solutions of beta blockers (in acetonitrile) and was then applied on urine samples (0.15; 0,2 and 0.4 mg/L). New calibration curves (5–25 mg/L), were prepared by using urine extract as solvent. Additionally, breakthrough volume, repeatability, and suitability of different calibration approaches (beta blockers in acetonitrile or urine extract) for urine samples was also tested. This method was successfully used to determine bisoprolol, metoprolol, and propranolol, in concentraction at least 0.2 mg/L. The following best extraction recoveries were calculated from the determination in TIC mode: (85.0 ± 2.4) % for metoprolol, (90.1 ± 6.0) % for propranolol, and (59.4 ± 8.3) % for bisoprolol.
Sekundarne ključne besede:	beta blockers;GC-MS;solid-phase extraction;urine samples;
Vrsta dela (COBISS):	Magistrsko delo/naloga
Študijski program:	1000375
Konec prepovedi (OpenAIRE):	1970-01-01
Komentar na gradivo:	Univ. v Ljubljani, Fak. za kemijo in kemijsko tehnologijo, smer Kemija
Strani:	49 str.
ID:	11638789