Title Nove kapilarno elektroforetske i kromatografske metode u analitici statina Title (english) New capillary electrophoresis and chromatography methods for analysis of statins Author Miranda Sertić Mentor Biljana Nigović (mentor)Committee member Irena Vedrina-Dragojević (predsjednik povjerenstva)Committee member Vlasta Drevenkar (član povjerenstva)Committee member Biserka Cetina Čižmek (član povjerenstva)Granter University of Zagreb Defense date and country 2013-05-03, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 615 - Pharmacology. Therapeutics. Toxicology Abstract Kardiovaskularne bolesti su vodeći uzrok smrtnosti u svijetu, a jednim od glavnih rizičnih čimbenika za njihov razvoj smatra se hiperlipidemija. Postoji nekoliko skupina hipolipemika, a najvažniji su statini, jedni od najčešće propisivanih lijekova uopće. Oni djeluju kao reverzibilni kompetitivni inhibitori HMG-CoA reduktaze, enzima koji katalizira limitirajući korak u biosintezi kolesterola. Svi statini još uvijek nemaju službene farmakopejske monografije, pa postoji velika potreba za razvojem analitičkih metoda za njihovu identifikaciju i određivanje sadržaja u aktivnim ljekovitim tvarima i gotovim ljekovitim oblicima. Terapija statinima je svakodnevna i dugoročna, pa je procjena njihove čistoće od velikog značaja, odnosno razvoj selektivnih i osjetljivih metoda za karakterizaciju, identifikaciju i određivanje sadržaja onečišćenja je neophodan.
Crvena fermentirana riža sadrži 14 monakolina koji imaju hipolipemički učinak, a najvažniji je monakolin K, poznat kao lovastatin. Na tržištu se nalaze brojni dodaci prehrani s crvenom fermentiranom rižom. Nažalost, nadležne nacionalne agencije diljem svijeta upozoravaju na lošu kvalitetu dodataka prehrani te potrebu za njihovim pojačanim nadzorom i redovitom kontrolom.
Cilj ovog istraživanja stoga je bio razviti nove, brze, selektivne, osjetljive, precizne i točne analitičke metode za identifikaciju i određivanje sadržaja statina, karakterizaciju i kvantifikaciju onečišćenja atorvastatina, najčešće korištenog lijeka iz skupine statina, te određivanje aktivnih i toksičnih sastavnica crvene fermentirane riže. U radu su korištene sofisticirane analitičke tehnike: kapilarna elektroforeza (CE), tekućinska kromatografija visoke djelotvornosti (HPLC) i masena spektrometrija (MS). Ukupno je razvijeno, validirano i uspješno primijenjeno 6 novih analitičkih metoda. Predložena CE metoda predstavlja jedinstvenu brzu analitičku metodu za analizu bilo kojeg od šest statina registriranih u Europskoj uniji. Određen je sadržaj četiriju onečišćenja atorvastatina te je strukturno karakterizirano i identificirano još osam prisutnih onečišćenja primjenom HPLC-DAD-MSn metode. Rezultati provedene analize proizvoda s crvenom fermentiranom rižom pokazuju značajna odstupanja u sadržaju lovastatina od deklariranih vrijednosti te između pojedinih serija proizvodnje, što upućuje na potrebu za strožom, detaljnijom i češćom kontrolom, u svrhu osiguranja djelotvornog, sigurnog i kvalitetnog proizvoda.
Abstract (english) Cardiovascular diseases are the leading cause of death in the world and one of the major risk factors for their development is considered hyperlipidemia. Statins are most commonly used drugs in the treatment of hyperlipidemia, and are one of the most often prescribed drugs in general. Statins act by competitively inhibiting HMG-CoA reductase, the rate limiting enzyme in the cholesterol biosynthesis. Not all statins have official pharmacopoeia monographs, so new analytical methods for their identification and determination in active pharmaceutical ingredients and finished drug products are highly required. Statin therapy is long-term and they are used on daily basis, so their purity assessment is of great importance. Hence, development of selective and sensitive methods for characterization, identification and determination of their impurities is indispensable.
Red fermented rice contatins 14 monacolins with hypolipemic effect, and the most important one is monacolin K, also known as lovastatin. There are numerous dietary supplements containing red fermented rice on the market. Unfortunately the relevant national agencies around the world warn of dietary supplements' poor quality and the need for their increased supervision and regular inspection.
Therefore, the aim of this research was to develop new, fast, selective, sensitive, precise and accurate analytical methods for the identification and determination of statins, characterization and quantification of atorvastatins impurities, which is the most commonly used statin drug, and determination of active and toxic ingredients in red fermented rice. Highly sophisticated analytical techniques were used: capillary electrophoresis (CE), high performance liquid chromatography (HPLC) and mass spectrometry (MS). In total 6 new analytical methods were developed, validated and successfully applied. The proposed CE method represents a universal fast analytical method for the analysis of any of the six statins registered in the European Union. The content of four atorvastatin impurities was determined and eight other impurities were structurally characterized and identified by HPLC-DAD-MSn method. The results of the red fermented rice products analysis indicated significant deviations in lovastatin content from declared values and among different batches. This suggests the need for tighter, more detailed and more frequent control in order to ensure effectiveness, safety and quality of these products.
Keywords
statini
crvena fermentirana riža
kapilarna elektroforeza
tekućinska kromatografija visoke djelotvornosti
masena spektrometrija
Keywords (english)
statins
red fermented rice
capillary electrophoresis
high performance liquid chromatography
mass spectrometry
Language croatian URN:NBN urn:nbn:hr:163:060606 Study programme Title: Pharmacy and biochemistry Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2016-11-25 14:01:16
