000841735 001__ 841735 000841735 005__ 20210129232059.0 000841735 0247_ $$2doi$$a10.1016/j.jchromb.2017.12.009 000841735 0247_ $$2ISSN$$a0378-4347 000841735 0247_ $$2ISSN$$a1387-2273 000841735 0247_ $$2ISSN$$a1570-0232 000841735 0247_ $$2ISSN$$a1872-812X 000841735 0247_ $$2ISSN$$a1873-376X 000841735 0247_ $$2ISSN$$a1878-5603 000841735 0247_ $$2pmid$$apmid:29248770 000841735 0247_ $$2WOS$$aWOS:000423889300016 000841735 037__ $$aFZJ-2018-00043 000841735 082__ $$a540 000841735 1001_ $$0P:(DE-Juel1)142389$$aHupert, Michelle$$b0$$eFirst author$$ufzj 000841735 245__ $$aDevelopment and validation of an UHPLC-ESI-QTOF-MS method for quantification of the highly hydrophilic amyloid-β oligomer eliminating all- D -enantiomeric peptide RD2 in mouse plasma 000841735 260__ $$aNew York, NY [u.a.]$$bScience Direct$$c2018 000841735 3367_ $$2DRIVER$$aarticle 000841735 3367_ $$2DataCite$$aOutput Types/Journal article 000841735 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1514989551_27321 000841735 3367_ $$2BibTeX$$aARTICLE 000841735 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000841735 3367_ $$00$$2EndNote$$aJournal Article 000841735 520__ $$aDuring preclinical drug development, a method for quantification of unlabeled compounds in blood plasma samples from treatment or pharmacokinetic studies in mice is required. In the current work, a rapid, specific, sensitive and validated liquid chromatography mass-spectrometric UHPLC-ESI-QTOF-MS method was developed for the quantification of the therapeutic compound RD2 in mouse plasma. RD2 is an all-D-enantiomeric peptide developed for the treatment of Alzheimer’s disease, a progressive neurodegenerative disease finally leading to dementia. Due to RD2’s highly hydrophilic properties, the sample preparation and the chromatographic separation and quantification were very challenging. The chromatographic separation of RD2 and its internal standard were accomplished on an Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm particle size) within 6.5 min at 50 °C with a flow rate of 0.5 mL/min. Mobile phases consisted of water and acetonitrile with 1% formic acid and 0.025% heptafluorobutyric acid, respectively. Ions were generated by electrospray ionization (ESI) in the positive mode and the peptide was quantified by QTOF-MS. The developed extraction method for RD2 from mouse plasma revealed complete recovery. The linearity of the calibration curve was in the range of 5.3 ng/mL to 265 ng/mL (r2 > 0.999) with a lower limit of detection (LLOD) of 2.65 ng/mL and a lower limit of quantification (LLOQ) of 5.3 ng/mL. The intra-day and inter-day accuracy and precision of RD2 in plasma ranged from −0.54% to 2.21% and from 1.97% to 8.18%, respectively. Moreover, no matrix effects were observed and RD2 remained stable in extracted mouse plasma at different conditions. Using this validated bioanalytical method, plasma samples of unlabeled RD2 or placebo treated mice were analyzed. The herein developed UHPLC-ESI-QTOF-MS method is a suitable tool for the quantitative analysis of unlabeled RD2 in plasma samples of treated mice. 000841735 536__ $$0G:(DE-HGF)POF3-553$$a553 - Physical Basis of Diseases (POF3-553)$$cPOF3-553$$fPOF III$$x0 000841735 588__ $$aDataset connected to CrossRef 000841735 7001_ $$0P:(DE-Juel1)164354$$aElfgen, Anne$$b1$$eFirst author$$ufzj 000841735 7001_ $$0P:(DE-Juel1)166069$$aSchartmann, Elena$$b2$$ufzj 000841735 7001_ $$0P:(DE-Juel1)165908$$aSchemmert, Sarah$$b3$$ufzj 000841735 7001_ $$0P:(DE-HGF)0$$aBuscher, Brigitte$$b4 000841735 7001_ $$0P:(DE-Juel1)159137$$aKutzsche, Janine$$b5$$ufzj 000841735 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b6$$eCorresponding author$$ufzj 000841735 7001_ $$0P:(DE-Juel1)133853$$aSantiago-Schübel, Beatrix$$b7$$eCorresponding author$$ufzj 000841735 773__ $$0PERI:(DE-600)1491259-4$$a10.1016/j.jchromb.2017.12.009$$gVol. 1073, p. 123 - 129$$p123 - 129$$tJournal of chromatography / B$$v1073$$x1570-0232$$y2018 000841735 8564_ $$uhttps://juser.fz-juelich.de/record/841735/files/1-s2.0-S1570023217316562-main.pdf$$yRestricted 000841735 8564_ $$uhttps://juser.fz-juelich.de/record/841735/files/1-s2.0-S1570023217316562-main.gif?subformat=icon$$xicon$$yRestricted 000841735 8564_ $$uhttps://juser.fz-juelich.de/record/841735/files/1-s2.0-S1570023217316562-main.jpg?subformat=icon-1440$$xicon-1440$$yRestricted 000841735 8564_ $$uhttps://juser.fz-juelich.de/record/841735/files/1-s2.0-S1570023217316562-main.jpg?subformat=icon-180$$xicon-180$$yRestricted 000841735 8564_ $$uhttps://juser.fz-juelich.de/record/841735/files/1-s2.0-S1570023217316562-main.jpg?subformat=icon-640$$xicon-640$$yRestricted 000841735 8564_ $$uhttps://juser.fz-juelich.de/record/841735/files/1-s2.0-S1570023217316562-main.pdf?subformat=pdfa$$xpdfa$$yRestricted 000841735 909CO $$ooai:juser.fz-juelich.de:841735$$pVDB 000841735 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)142389$$aForschungszentrum Jülich$$b0$$kFZJ 000841735 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)164354$$aForschungszentrum Jülich$$b1$$kFZJ 000841735 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)166069$$aForschungszentrum Jülich$$b2$$kFZJ 000841735 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)165908$$aForschungszentrum Jülich$$b3$$kFZJ 000841735 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)159137$$aForschungszentrum Jülich$$b5$$kFZJ 000841735 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)132029$$aForschungszentrum Jülich$$b6$$kFZJ 000841735 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)133853$$aForschungszentrum Jülich$$b7$$kFZJ 000841735 9131_ $$0G:(DE-HGF)POF3-553$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lBioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vPhysical Basis of Diseases$$x0 000841735 9141_ $$y2018 000841735 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz 000841735 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000841735 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000841735 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000841735 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search 000841735 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC 000841735 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000841735 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000841735 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000841735 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000841735 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000841735 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000841735 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ CHROMATOGR B : 2015 000841735 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5 000841735 920__ $$lyes 000841735 9201_ $$0I:(DE-Juel1)ZEA-3-20090406$$kZEA-3$$lAnalytik$$x0 000841735 9201_ $$0I:(DE-Juel1)ICS-6-20110106$$kICS-6$$lStrukturbiochemie $$x1 000841735 980__ $$ajournal 000841735 980__ $$aVDB 000841735 980__ $$aI:(DE-Juel1)ZEA-3-20090406 000841735 980__ $$aI:(DE-Juel1)ICS-6-20110106 000841735 980__ $$aUNRESTRICTED 000841735 981__ $$aI:(DE-Juel1)IBI-7-20200312