Show simple item record

dc.creatorIliou, Katerina
dc.creatorMalenović, Anđelija
dc.creatorLoukas, Yannis L.
dc.creatorDotsikas, Yannis
dc.date.accessioned2019-09-02T12:07:11Z
dc.date.available2019-09-02T12:07:11Z
dc.date.issued2018
dc.identifier.issn0731-7085
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3190
dc.description.abstractA novel Liquid Chromatography-tandem mass spectrometry (LC-MS/MS) method is presented for the quantitative determination of two potential genotoxic impurities (PGIs) in rabeprazole active pharmaceutical ingredient (API). In order to overcome the analytical challenges in the trace analysis of PGIs, a development procedure supported by Quality-by-Design (Q1313) principles was evaluated. The efficient separation between rabeprazole and the two PGIs in the shortest analysis time was set as the defined analytical target profile (ATP) and to this purpose utilization of a switching valve allowed the flow to be sent to waste when rabeprazole was eluted. The selected critical quality attributes (CQAs) were the separation criterion s between the critical peak pair and the capacity factor k of the last eluted compound. The effect of the following critical process parameters (CPPs) on the CQAs was studied: %ACN content, the pH and the concentration of the buffer salt in the mobile phase, as well as the stationary phase of the analytical column. D-Optimal design was implemented to set the plan of experiments with UV detector. In order to define the design space, Monte Carlo simulations with 5000 iterations were performed. Acceptance criteria were met for Cs column (50 x 4 mm, 5 p.m), and the region having probability pi >= 95% to achieve satisfactory values of all defined CQAs was computed. The working point was selected with the mobile phase consisting of ACN, ammonium formate 11 mM at a ratio 31/69 v/v with pH-6,8 for the water phase. The LC protocol was transferred to LC-MS/MS and validated according to ICH guidelines.en
dc.publisherElsevier Science BV, Amsterdam
dc.rightsrestrictedAccess
dc.sourceJournal of Pharmaceutical and Biomedical Analysis
dc.subjectRabeprazoleen
dc.subjectPotential genotoxic impuritiesen
dc.subjectQuality-by-designen
dc.subjectD-Optimal designen
dc.subjectLC-MS/MSen
dc.titleAnalysis of potential genotoxic impurities in rabeprazole active pharmaceutical ingredient via Liquid Chromatography-tandem Mass Spectrometry, following quality-by-design principles for method developmenten
dc.typearticle
dc.rights.licenseARR
dcterms.abstractДотсикас, Yаннис; Маленовић, Aнђелија; Лоукас, Yаннис Л.; Илиоу, Катерина;
dc.citation.volume149
dc.citation.spage410
dc.citation.epage418
dc.citation.other149: 410-418
dc.citation.rankM21
dc.identifier.wos000424315700052
dc.identifier.doi10.1016/j.jpba.2017.11.037
dc.identifier.pmid29154196
dc.identifier.scopus2-s2.0-85034112739
dc.identifier.rcubconv_4045
dc.type.versionpublishedVersion


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record