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@ARTICLE{Jonas:1055046,
author = {Jonas, Alissa and Gering, Ian and Schartmann, Elena and
Schemmert, Sarah and Willbold, Dieter and Santiago-Schübel,
Beatrix and Kutzsche, Janine},
title = {{D}evelopment and {V}alidation of an
{UHPLC}-{ESI}-{QTOF}-{MS} {M}ethod {A}ccording to the {ICH}
{M}10 {G}uideline for {Q}uantification of the {C}linical
{D}rug {C}andidate {RD}2 in the {M}ouse {B}rain},
journal = {Analytica},
volume = {7},
number = {1},
issn = {2673-4532},
address = {Basel},
publisher = {MDPI},
reportid = {FZJ-2026-01838},
pages = {15 -},
year = {2026},
abstract = {The all-D-enantiomeric-peptide RD2 was developed for the
treatment of Alzheimer’s disease. This study aimed to
develop a specific and highly sensitive liquid
chromatographymass-spectrometric (UHPLC-ESI-QTOF) method for
quantifying RD2 in the mouse brainand to validate it
according to the ICH M10 guideline to investigate the
pharmacokinetic profile of RD2 in its target organ. Sample
preparation, chromatographic separation and quantification
were very challenging due to RD2’s highly hydrophilic
properties, the complex matrix and the required lower limit
of quantification (LLOQ). Chromatographic separation was
performed on an Acquity UPLC BEH C18 column (2.1 × 100 mm,
1.7 μm particle size) within 5 min at 50 ◦C with a flow
rate of 0.5 mL·min−1. Mobile phasesconsisted of water and
acetonitrile with $0.2\%$ formic acid and $0.015\%$
heptafluorobutyric acid. Ions were generated by electrospray
ionization in the positive mode, and RD2 was quantified by
QTOF-MS. The developed extraction method revealed complete
recovery.The linearity of the calibration curve was in the
range of 2 ng·mL−1 to 500 ng·mL−1 (R2 > 0.99) with a
LLOQ of 5 ng·mL−1. The intraday and interday accuracy and
precision ranged from $0.4\%$ to $12.2\%$ and from $1.0\%$
to $12.0\%.$ RD2 remained stable in thefreshly homogenized
brain even after several freeze–thaw cycles, but stability
decreased over time during long-term storage at −80 ◦C.
Using this validated method, RD2-spiked brain homogenate
samples and samples of a pharmacokinetic study with RD2 in
micewere analyzed.},
cin = {IBI-7},
ddc = {540},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
doi = {10.3390/analytica7010015},
url = {https://juser.fz-juelich.de/record/1055046},
}