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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},
}