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dc.contributor.authorReimerova, Petra
dc.contributor.authorStariat, Jan
dc.contributor.authorPiskackova, Hana Bavlovic
dc.contributor.authorJansova, Hana
dc.contributor.authorRoh, Jaroslav
dc.contributor.authorKalinowski, Danuta S
dc.contributor.authorMachacek, Miloslav
dc.contributor.authorSimunek, Tomas
dc.contributor.authorRichardson, Des R
dc.contributor.authorSterbova-Kovarikova, Petra
dc.date.accessioned2021-04-23T04:35:25Z
dc.date.available2021-04-23T04:35:25Z
dc.date.issued2019
dc.identifier.issn1618-2642
dc.identifier.doi10.1007/s00216-019-01681-w
dc.identifier.urihttp://hdl.handle.net/10072/403960
dc.description.abstractSolid-phase microextraction (SPME) is an alternative method to dialysis and ultrafiltration for the determination of plasma protein binding (PPB) of drugs. It is particularly advantageous for complicated analytes where standard methods are not applicable. Di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) is a lead compound of novel thiosemicarbazone anti-cancer drugs, which entered clinical trials in 2016. However, this agent exhibited non-specific binding on filtration membranes and had intrinsic chelation activity, which precluded standard PPB methods. In this study, using a simple and fast procedure, we prepared novel SPME fibers for extraction of DpC based on a metal-free, silicon string support, covered with C18 sorbent. Reproducibility of the preparation process was demonstrated by the percent relative standard deviation (RSD) of ≤ 9.2% of the amount of DpC extracted from PBS by several independently prepared fibers. The SPME procedure was optimized by evaluating extraction and desorption time profiles. Suitability of the optimized protocol was verified by examining reproducibility, linearity, and recovery of DpC extracted from PBS or plasma. All samples extracted by SPME were analyzed using an optimized and validated UHPLC-MS/MS method. The developed procedure was applied to the in vitro determination of PPB of DpC at two clinically relevant concentrations (500 and 1000 ng/mL). These studies showed that DpC is highly bound to plasma proteins (PPB ≥ 88%) and this did not differ significantly between both concentrations tested. This investigation provides novel data in the applicability of SPME for the determination of PPB of chelators, as well as useful information for the clinical development of DpC.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherSpringer
dc.relation.ispartofpagefrom2383
dc.relation.ispartofpageto2394
dc.relation.ispartofissue11
dc.relation.ispartofjournalAnalytical and Bioanalytical Chemistry
dc.relation.ispartofvolume411
dc.subject.fieldofresearchChemical sciences
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchEngineering
dc.subject.fieldofresearchcode34
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode40
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsPhysical Sciences
dc.subject.keywordsBiochemical Research Methods
dc.subject.keywordsChemistry, Analytical
dc.titleNovel SPME fibers based on a plastic support for determination of plasma protein binding of thiosemicarbazone metal chelators: a case example of DpC, an anti-cancer drug that entered clinical trials
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationReimerova, P; Stariat, J; Piskackova, HB; Jansova, H; Roh, J; Kalinowski, DS; Machacek, M; Simunek, T; Richardson, DR; Sterbova-Kovarikova, P, Novel SPME fibers based on a plastic support for determination of plasma protein binding of thiosemicarbazone metal chelators: a case example of DpC, an anti-cancer drug that entered clinical trials, Analytical and Bioanalytical Chemistry, 2019, 411 (11), pp. 2383-2394
dcterms.dateAccepted2019-02-07
dc.date.updated2021-04-23T04:34:12Z
gro.hasfulltextNo Full Text
gro.griffith.authorRichardson, Des R.


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