Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
4220311
Reference Type
Journal Article
Title
Development 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
Author(s)
Hupert, M; Elfgen, A; Schartmann, E; Schemmert, S; Buscher, B; Kutzsche, J; Willbold, D; Santiago-Schübel, B
Year
2018
Is Peer Reviewed?
Yes
Journal
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
ISSN:
1570-0232
EISSN:
1873-376X
Publisher
Elsevier B.V.
Volume
1073
Page Numbers
123-129
Language
English
PMID
29248770
DOI
10.1016/j.jchromb.2017.12.009
Web of Science Id
WOS:000423889300016
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.
Keywords
UHPLC-ESI-QTOF-MS; Mouse plasma; D-peptide; Amyloid-beta peptide; Therapeutic compound; Alzheimer's disease
Tags
PFAS
•
Additional PFAS (formerly XAgency)
•
PFAS 150
Literature Search August 2019
PubMed
Web of Science
Other sources
Identified after chem tag updates in SWIFT Review
Screened Studies
Excluded
Exclude (TIAB)
Perfluorobutanoic acid
•
PFBA
Literature Search
Pubmed
WOS
Literature Search Update 5/2019
WOS
Scopus: April 2021
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity