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@ARTICLE{Hupert:841735,
      author       = {Hupert, Michelle and Elfgen, Anne and Schartmann, Elena and
                      Schemmert, Sarah and Buscher, Brigitte and Kutzsche, Janine
                      and Willbold, Dieter and Santiago-Schübel, Beatrix},
      title        = {{D}evelopment and validation of an
                      {UHPLC}-{ESI}-{QTOF}-{MS} method for quantification of the
                      highly hydrophilic amyloid-β oligomer eliminating all- {D}
                      -enantiomeric peptide {RD}2 in mouse plasma},
      journal      = {Journal of chromatography / B},
      volume       = {1073},
      issn         = {1570-0232},
      address      = {New York, NY [u.a.]},
      publisher    = {Science Direct},
      reportid     = {FZJ-2018-00043},
      pages        = {123 - 129},
      year         = {2018},
      abstract     = {During 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.},
      cin          = {ZEA-3 / ICS-6},
      ddc          = {540},
      cid          = {I:(DE-Juel1)ZEA-3-20090406 / I:(DE-Juel1)ICS-6-20110106},
      pnm          = {553 - Physical Basis of Diseases (POF3-553)},
      pid          = {G:(DE-HGF)POF3-553},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29248770},
      UT           = {WOS:000423889300016},
      doi          = {10.1016/j.jchromb.2017.12.009},
      url          = {https://juser.fz-juelich.de/record/841735},
}