Show simple item record

Analiza degradacionih proizvoda donepezila primenom tečne hromatografije i tečne hromatografije-masene spektrometrije

dc.creatorMladenović, Aleksandar R.
dc.creatorJadranin, Milka
dc.creatorPavlović, Aleksandar D.
dc.creatorPetrović, Slobodan D.
dc.creatorDrmanić, Saša Ž.
dc.creatorAvramov Ivić, Milka
dc.creatorMijin, Dušan
dc.date.accessioned2019-01-30T17:45:47Z
dc.date.available2019-01-30T17:45:47Z
dc.date.issued2015
dc.identifier.issn1451-9372
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/1731
dc.description.abstractThis study describes the investigation of degradation products of donepezil (DP) using a stability-indicating RP-HPLC method for determination of donepezil, which is a centrally acting reversible acetyl cholinesterase inhibitor. In order to investigate the stability of the drug and formed degradation products, a forced degradation study of the drug sample and finished product under different forced degradation conditions was conducted. Donepezil hydrochloride and donepezil tablets were subjected to stress degradation conditions recommended by the International Conference on Harmonization (ICH). Donepezil hydrochloride solutions were subjected to acid and alkali hydrolysis, chemical oxidation and thermal degradation. Significant degradation was observed under alkali hydrolysis and oxidative degradation conditions. Additional degradation products were observed under the conditions of oxidative degradation. The degradation products observed during forced degradation studies were monitored using the developed high performance liquid chromatography (HPLC) method. The parent method was modified in order to obtain LC-MS compatible method, which was used to identify the degradation products from forced degradation samples using high resolution mass spectrometry. The mass spectrum provided the precise mass from which the molecular formula of the drug substance and formed degradation products was derived, and proved the specificity of the method unambiguously.en
dc.description.abstractProučavanje degradacionih proizvoda donepezila je izvršeno korišćenjem RP-HPLC metode za određivanje stabilnosti donepezila, leka koji pripada grupi reverzibilnih inhibitora acetilholinesteraze. U cilju ispitivanja stabilnosti leka i njegovih degradacionih proizvoda sprovedena je studija forsirane degradacije čiste supstance kao i farmaceutskog proizvoda pod različitim uslovima. Donepezil-hidrohlorid i donepezil tablete su podvrgnuti različitim uslovima degradacije prema preporukama Internacionalne konferencije za harmonizaciju. Rastvori donepezil-hidrohlorida su podvrgnuti kiseloj i baznoj hidrolizi, hemijskoj oksidaciji i termalnoj degradaciji. Pri baznoj hidrolizi i hemijskoj oksidaciji uočena je značajna degradacija polaznog molekula. Oksidativnom degradacijom nastaju i proizvodi koji nisu uočeni kod ostalih postupaka forsirane degradacije. Nastali proizvodi analizirani su novorazvijenom HPLC metodom. Osnovna metoda je modifikovana u cilju dobijanja LC-MS kompatibilne metode kako bi se identifikovali nastali degradacioni proizvodi. Na osnovu resultata dobijenih masenom spektrometrijom dobijene su tačne mase proizvoda degradacije, čime je omogućeno određivanje njihovih molekulskih formula.sr
dc.publisherAssociation of the Chemical Engineers of Serbia
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172013/RS//
dc.rightsopenAccess
dc.sourceChemical Industry and Chemical Engineering Quarterly / CICEQ
dc.subjectdonepezil hydrochlorideen
dc.subjectforced degradationen
dc.subjectstability-indicating HPLC methoden
dc.subjectliquid chromatography-mass spectrometryen
dc.subjectdonepezil-hidrohloridsr
dc.subjectforsirana degradacijasr
dc.subjectHPLC metoda za određivanje stabilnostisr
dc.subjecttečna hromatografija-masena spektrometrijasr
dc.titleLiquid chromatography and liquid chromatography-mass spectrometry analysis of donepezil degradation productsen
dc.titleAnaliza degradacionih proizvoda donepezila primenom tečne hromatografije i tečne hromatografije-masene spektrometrijesr
dc.typearticle
dc.rights.licenseBY-NC-ND
dcterms.abstractМладеновић, Aлександар Р.; Петровић, Слободан Д.; Дрманић, Саша Ж.; Мијин, Душан Ж.; Јадранин, Милка; Павловић, Aлександар Д.; Aврамов Ивић, Милка; Aнализа деградационих производа донепезила применом течне хроматографије и течне хроматографије-масене спектрометрије; Aнализа деградационих производа донепезила применом течне хроматографије и течне хроматографије-масене спектрометрије;
dc.citation.volume21
dc.citation.issue3
dc.citation.spage447
dc.citation.epage455
dc.citation.other21(3): 447-455
dc.citation.rankM23
dc.identifier.doi10.2298/CICEQ141023047M
dc.identifier.rcubConv_529
dc.identifier.fulltexthttp://cer.ihtm.bg.ac.rs//bitstream/id/8175/1729.pdf
dc.identifier.scopus2-s2.0-84940536168
dc.identifier.wos000360690200009
dc.type.versionpublishedVersion


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record