Time-course of kynurenic acid concentration in mouse serum following the administration of a novel kynurenic acid analog

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Abstract

The changes in concentration of kynurenic acid (KYNA) in different biological samples are of great interest in the pathomechanism and medication of several disorders, and especially those affecting the nervous system. Besides the recent pharmaceutical advances targeting the kynurenine pathway, there is a constant need for further drug development through the synthesis of novel analogs. Reliable analytical methods should be set up to monitor the metabolism and effects of these analogs in both preclinical experiments and human studies. Following a sample preparation procedure based on protein precipitation, new high-performance liquid chromatographic methods with fluorescence and mass spectrometric detection were developed for the determination of KYNA and a novel KYNA analog (N-(2- N,. N-dimethylaminoethyl)-4-oxo-1. H-quinoline-2-carboxamide hydrochloride; KYNA amide) in mouse serum samples. The analytical parameters obtained in the validation procedure suggest that the developed method with mass spectrometric detection is simple, fast, accurate and suitable for the measurement of KYNA and its analogs. The results reveal the good in vivo stability of the novel KYNA amide.

Original languageEnglish
Pages (from-to)540-543
Number of pages4
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume55
Issue number3
DOIs
Publication statusPublished - Jun 1 2011

Fingerprint

Kynurenic Acid
Serum
Amides
Kynurenine
Neurology
Metabolism
Pharmaceutical Preparations
Nervous System
Fluorescence
Liquids

Keywords

  • High-performance liquid chromatography
  • Kynurenic acid
  • Kynurenic acid analog
  • Mass spectrometry
  • Pharmacokinetic study

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Spectroscopy
  • Clinical Biochemistry

Cite this

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abstract = "The changes in concentration of kynurenic acid (KYNA) in different biological samples are of great interest in the pathomechanism and medication of several disorders, and especially those affecting the nervous system. Besides the recent pharmaceutical advances targeting the kynurenine pathway, there is a constant need for further drug development through the synthesis of novel analogs. Reliable analytical methods should be set up to monitor the metabolism and effects of these analogs in both preclinical experiments and human studies. Following a sample preparation procedure based on protein precipitation, new high-performance liquid chromatographic methods with fluorescence and mass spectrometric detection were developed for the determination of KYNA and a novel KYNA analog (N-(2- N,. N-dimethylaminoethyl)-4-oxo-1. H-quinoline-2-carboxamide hydrochloride; KYNA amide) in mouse serum samples. The analytical parameters obtained in the validation procedure suggest that the developed method with mass spectrometric detection is simple, fast, accurate and suitable for the measurement of KYNA and its analogs. The results reveal the good in vivo stability of the novel KYNA amide.",
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author = "D{\'e}nes Z{\'a}dori and I. Ilisz and P. Kliv{\'e}nyi and I. Szatm{\'a}ri and F. F{\"u}l{\"o}p and J. Toldi and L. V{\'e}csei and A. P{\'e}ter",
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AU - Zádori, Dénes

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AU - Klivényi, P.

AU - Szatmári, I.

AU - Fülöp, F.

AU - Toldi, J.

AU - Vécsei, L.

AU - Péter, A.

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N2 - The changes in concentration of kynurenic acid (KYNA) in different biological samples are of great interest in the pathomechanism and medication of several disorders, and especially those affecting the nervous system. Besides the recent pharmaceutical advances targeting the kynurenine pathway, there is a constant need for further drug development through the synthesis of novel analogs. Reliable analytical methods should be set up to monitor the metabolism and effects of these analogs in both preclinical experiments and human studies. Following a sample preparation procedure based on protein precipitation, new high-performance liquid chromatographic methods with fluorescence and mass spectrometric detection were developed for the determination of KYNA and a novel KYNA analog (N-(2- N,. N-dimethylaminoethyl)-4-oxo-1. H-quinoline-2-carboxamide hydrochloride; KYNA amide) in mouse serum samples. The analytical parameters obtained in the validation procedure suggest that the developed method with mass spectrometric detection is simple, fast, accurate and suitable for the measurement of KYNA and its analogs. The results reveal the good in vivo stability of the novel KYNA amide.

AB - The changes in concentration of kynurenic acid (KYNA) in different biological samples are of great interest in the pathomechanism and medication of several disorders, and especially those affecting the nervous system. Besides the recent pharmaceutical advances targeting the kynurenine pathway, there is a constant need for further drug development through the synthesis of novel analogs. Reliable analytical methods should be set up to monitor the metabolism and effects of these analogs in both preclinical experiments and human studies. Following a sample preparation procedure based on protein precipitation, new high-performance liquid chromatographic methods with fluorescence and mass spectrometric detection were developed for the determination of KYNA and a novel KYNA analog (N-(2- N,. N-dimethylaminoethyl)-4-oxo-1. H-quinoline-2-carboxamide hydrochloride; KYNA amide) in mouse serum samples. The analytical parameters obtained in the validation procedure suggest that the developed method with mass spectrometric detection is simple, fast, accurate and suitable for the measurement of KYNA and its analogs. The results reveal the good in vivo stability of the novel KYNA amide.

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