TY - JOUR
T1 - Exploratory pharmacokinetics and brain distribution study of a neuropeptide FF antagonist by liquid chromatography/atmospheric pressure ionization tandem mass spectrometry
AU - Prokai, Laszlo
AU - Zharikova, Alevtina D.
AU - Janáky, Tamás
AU - Prokai-Tatrai, Katalin
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034534885&partnerID=8YFLogxK
U2 - 10.1002/1097-0231(20001230)14:24<2412::AID-RCM180>3.0.CO;2-3
DO - 10.1002/1097-0231(20001230)14:24<2412::AID-RCM180>3.0.CO;2-3
M3 - Article
C2 - 11114059
AN - SCOPUS:0034534885
SN - 0951-4198
VL - 14
SP - 2412
EP - 2418
JO - Rapid Communications in Mass Spectrometry
JF - Rapid Communications in Mass Spectrometry
IS - 24
ER -