Exploratory pharmacokinetics and brain distribution study of a neuropeptide FF antagonist by liquid chromatography/atmospheric pressure ionization tandem mass spectrometry

Laszlo Prokai, Alevtina D. Zharikova, Tamás Janáky, Katalin Prokai-Tatrai

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Dansyl-Pro-Gln-Arg-NH2, an N-terminally modified tripeptide amide and a putative neuropeptide FF antagonist, was amenable to both positive-ion ESI and APCL. The protonated molecule yielded several fragment ions upon collision-induced dissociation in a quadrupole ion trap instrument for the development of LC/MS/MS assay methods. ESI clearly outperformed APCI in limits of detection, and was the method of choice for coupling with narrow-bore reversed-phase liquid chromatography to assess the pharmacokinetic profile and brain concentration of the neuropeptide FF antagonist in experimental animals. While plasma could be analyzed after rapid sample preparation, brain tissue required cleanup (solid phase extraction) and preconcentration before injection, and the assay was prone to matrix interference. This study indicated a rapid disappearance of dansyl-Pro-Gln-Arg-NH2 from the plasma and the brain, and modest CNS bioavailability after intravenous administration to rats. Copyright (C) 2000 John Wiley and Sons, Ltd.

Original languageEnglish
Pages (from-to)2412-2418
Number of pages7
JournalRapid Communications in Mass Spectrometry
Volume14
Issue number24
DOIs
StatePublished - 1 Dec 2000

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