Bioanalytical method development and validation of MES207, a neuropeptide FF receptor antagonist, and its application in preclinical pharmacokinetics.
MES207
NPFF antagonist
Pharmacokinetics
UPLC-MS/MS
Journal
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
ISSN: 1873-376X
Titre abrégé: J Chromatogr B Analyt Technol Biomed Life Sci
Pays: Netherlands
ID NLM: 101139554
Informations de publication
Date de publication:
15 Dec 2019
15 Dec 2019
Historique:
received:
14
08
2019
revised:
23
10
2019
accepted:
01
11
2019
pubmed:
4
12
2019
medline:
8
2
2020
entrez:
3
12
2019
Statut:
ppublish
Résumé
The nonpeptide small molecule, MES207, exhibits 17-fold preferential binding to the neuropeptide FF receptor 1 (NPFFR1) over NPFFR2 and shows antagonist functionality at NPFF receptors. In order to further the development of MES207 as a NPFFR1 probe, an UPLC-MS/MS bioanalytical method was developed and validated to quantify MES207 in rat plasma for a linearity range of 3-200 ng/mL. The method was applied in the analysis of the plasma, brain, and urine samples collected during pharmacokinetic studies in healthy male and female Sprague Dawley rats. The animals were dosed through oral gavage (50 mg/kg) and intravenously (2.5 mg/kg). Test samples were analyzed using the validated bioanalytical method to generate plasma concentration-time profiles. The results were further subjected to non-compartmental analysis using Phoenix 6.4®. MES207 exhibits a large volume of distribution (1.2 ± 0.6 L), high clearance (0.8 ± 0.1 L/h), and a poor oral bioavailability (1.7 ± 0.4%). The compound also showed a multiple peak phenomenon with a very short absorption phase. It appears that gender does not significantly influence the differences in pharmacokinetic parameters of this NPFF probe.
Identifiants
pubmed: 31790916
pii: S1570-0232(19)31229-2
doi: 10.1016/j.jchromb.2019.121875
pmc: PMC7027589
mid: NIHMS1545210
pii:
doi:
Substances chimiques
1-benzyl-N-(2-guanidinoethyl)-4-(phenylamino)piperidine-4-carboxamide
0
Guanidines
0
Piperidines
0
Receptors, Neuropeptide
0
neuropeptide FF receptor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
121875Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM104932
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA034777
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA047855
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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