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dc.creatorSljivić, Jasmina
dc.creatorProtić, Ana
dc.creatorOtašević, Biljana
dc.creatorGolubović, Jelena
dc.creatorZečević, Mira
dc.creatorKrmar, Jovana
dc.date.accessioned2019-09-02T12:00:05Z
dc.date.available2019-09-02T12:00:05Z
dc.date.issued2017
dc.identifier.issn0021-9665
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2905
dc.description.abstractMulticriteria optimization methodology was applied in development of UHPLC-UV-MS method for separation of cilazapril, hydrochlorothiazide and their degradation products. This method is also applicable for analysis of cilazapril, hydrochlorothiazide and their degradation products in combined tablet formulation. Prior to method optimization forced degradation studies were conducted. Cilazapril and hydrochlorothiazide were subjected to acidic (0.1, 0.5 and 1.0M HCl), basic (0.1, 0.5 and 1.0M NaOH), thermal (70 degrees C), oxidative (3-30% H2O2) degradation and photodegradation (day light). Cilazapril appeared to be unstable toward acid and base and resulted in formation of cilazaprilat. Hydrochlorothiazide significantly degraded after acid, base and thermal hydrolysis and formed degradation product was 4-amino-6-chlorobenzene-1.3-disulfonamide. For both substances, after oxidative degradation unknown products have arisen. Initial percentage of acetonitrile in mobile phase, final percentage of acetonitrile in mobile phase, time of gradient elution and column temperature were defined as variables to be optimized toward two chromatographic responses by means of central composite design and Derringer's desirability function. The satisfactory chromatographic analysis was achieved on Kinetex C18 (2.6 mu m, 50 x 2.1 mm) column with temperature set at 25 degrees C. The final mobile phase consisted of acetonitrile and 20mM ammonium formate buffer (pH adjusted to 8.5). The flow rate of the mobile phase was 400 mu L min(-1) and it was pumped in a gradient elution mode.en
dc.publisherOxford Univ Press Inc, Cary
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172033/RS//
dc.rightsopenAccess
dc.sourceJournal of Chromatographic Science
dc.titleMulticriteria Optimization Methodology in Stability-Indicating Method Development of Cilazapril and Hydrochlorothiazideen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractГолубовић, Јелена; Зечевић, Мира; Сљивић, Јасмина; Протић, Aна; Оташевић, Биљана; Крмар, Јована;
dc.citation.volume55
dc.citation.issue6
dc.citation.spage625
dc.citation.epage637
dc.citation.other55(6): 625-637
dc.citation.rankM23
dc.identifier.wos000404619700006
dc.identifier.doi10.1093/chromsci/bmx018
dc.identifier.pmid28334985
dc.identifier.scopus2-s2.0-85024406870
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs//bitstream/id/1523/2903.pdf
dc.identifier.rcubconv_3799
dc.type.versionpublishedVersion


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