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dc.creatorTubić, Biljana K.
dc.creatorMarković, Bojan D.
dc.creatorVladimirov, Sandra S.
dc.creatorRistić, Slavica M.
dc.creatorIvković, Branka
dc.creatorSavić, Miroslav M.
dc.creatorPoljarević, Jelena
dc.creatorSabo, Tibor
dc.date.accessioned2018-11-22T00:40:07Z
dc.date.available2018-11-22T00:40:07Z
dc.date.issued2017
dc.identifier.issn1233-2356
dc.identifier.urihttp://cherry.chem.bg.ac.rs/handle/123456789/2459
dc.description.abstractA series of new (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (LOQ) was 1.3 ng mL(-1) for DE-EDCP and 0.3 mu g mL(-1) for EDCP. The calibration curves were linear over the concentration range of 1.3-26.7 ng mL(-1) and 0.3-6.7 mu g mL(-1) for DE-EDCP and EDCP, respectively. Precision (%CV) and accuracy (% RE) for DE-EDCP and EDCP ranged from 3.5% to 16.0% and from 1.8% to 14.4%, respectively. The validation process was performed in accordance with the regulatory guidance/guideline, and all of the obtained results met the established acceptance criteria. The newly developed and validated UHPLC-MS/MS method is rapid, sensitive, and selective, and it can be successfully applied to drug monitoring in nonclinical studies.en
dc.publisherAkademiai Kiado Rt, Budapest
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172041/RS//
dc.rightsopenAccess
dc.sourceActa Chromatographica
dc.subjectUHPLC-MS/MSen
dc.subjectprotein precipitation sample preparationen
dc.subject(S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl) propanoic acid estersen
dc.subjectcytotoxic activityen
dc.subjectmetaboliteen
dc.titleHighly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serumen
dc.typearticle
dc.rights.licenseBY
dcterms.abstractСабо, Тибор; Тубиц, Биљана К.; Марковиц, Бојан Д.; Владимиров, Сандра С.; Ристиц, Славица М.; Ивковиц, Бранка М.; Савиц, Мирослав М.; Пољаревић, Јелена;
dc.citation.volume29
dc.citation.issue2
dc.citation.spage235
dc.citation.epage252
dc.identifier.wos000401612800007
dc.identifier.doi10.1556/1326.2017.29.2.7
dc.citation.other29(2): 235-252
dc.citation.rankM23
dc.type.versionpublishedVersion
dc.identifier.scopus2-s2.0-85020063021
dc.identifier.fulltexthttp://cherry.chem.bg.ac.rs/bitstream/id/9415/2457.pdf
dc.identifier.rcubKon_3275


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