Blood-brain barrier penetration of 3-aminopropyl-n-butylphosphinic acid (CGP 36742) in rat brain by microdialysis/mass spectrometry

Per E. Andrén, Mark Emmett, Beverly B. DaGue, Anne Françoise Steulet, Peter Waldmeier, Richard M. Caprioli

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The detection and quantitation of the novel drug 3-aminopropyl-n- butylphosphinic acid (APBP), also known as CGP 36742, was performed in vivo using microdialysis and tandem mass spectrometry. This drug is a GABA-B antagonist with high specificity for GABA-B receptors. Animals received doses of 100, 200, 500 and 1000 mg kg-1 of the drug either intravenously or per os (p.o.). Microdialysis probes, placed by stereotaxis in either the frontal cortex or third ventricle of the rat, were used to collect dialyzate samples over several hours. Samples were then analyzed by micro-electrospray tandem mass spectrometry to achieve a molecular mass and structure specific analysis. For example, animals receiving a dose of 100 mg kg-1 p.o. showed a peak concentration of approximately 10 μM in the dialyzate. For comparison, tissue and plasma samples of the drug were measured under the same conditions using gas chromatography/mass spectrometry. This work demonstrates that the microdialysis technique in combination with the molecular specificity and high sensitivity of micro-electrospray tandem mass spectrometry can be used to study the time course of the appearance of unmodified drug in the brain of a single animal.

Original languageEnglish (US)
Pages (from-to)281-287
Number of pages7
JournalJournal of Mass Spectrometry
Volume33
Issue number3
DOIs
StatePublished - Mar 1998
Externally publishedYes

Fingerprint

blood-brain barrier
Microdialysis
Blood-Brain Barrier
rats
brain
Mass spectrometry
Rats
Brain
Mass Spectrometry
drugs
mass spectroscopy
penetration
Tandem Mass Spectrometry
acids
Animals
Acids
animals
Pharmaceutical Preparations
Dialysis Solutions
GABA-B Receptor Antagonists

Keywords

  • 3- aminopropyl-n-butylphosphinic acid
  • CGP 36742
  • GABA antagonist
  • Mass spectrometry
  • Microdialysis
  • Pharmacokinetics

ASJC Scopus subject areas

  • Organic Chemistry
  • Spectroscopy
  • Biophysics

Cite this

Blood-brain barrier penetration of 3-aminopropyl-n-butylphosphinic acid (CGP 36742) in rat brain by microdialysis/mass spectrometry. / Andrén, Per E.; Emmett, Mark; DaGue, Beverly B.; Steulet, Anne Françoise; Waldmeier, Peter; Caprioli, Richard M.

In: Journal of Mass Spectrometry, Vol. 33, No. 3, 03.1998, p. 281-287.

Research output: Contribution to journalArticle

Andrén, Per E. ; Emmett, Mark ; DaGue, Beverly B. ; Steulet, Anne Françoise ; Waldmeier, Peter ; Caprioli, Richard M. / Blood-brain barrier penetration of 3-aminopropyl-n-butylphosphinic acid (CGP 36742) in rat brain by microdialysis/mass spectrometry. In: Journal of Mass Spectrometry. 1998 ; Vol. 33, No. 3. pp. 281-287.
@article{76d00617df504483862965bd049239bd,
title = "Blood-brain barrier penetration of 3-aminopropyl-n-butylphosphinic acid (CGP 36742) in rat brain by microdialysis/mass spectrometry",
abstract = "The detection and quantitation of the novel drug 3-aminopropyl-n- butylphosphinic acid (APBP), also known as CGP 36742, was performed in vivo using microdialysis and tandem mass spectrometry. This drug is a GABA-B antagonist with high specificity for GABA-B receptors. Animals received doses of 100, 200, 500 and 1000 mg kg-1 of the drug either intravenously or per os (p.o.). Microdialysis probes, placed by stereotaxis in either the frontal cortex or third ventricle of the rat, were used to collect dialyzate samples over several hours. Samples were then analyzed by micro-electrospray tandem mass spectrometry to achieve a molecular mass and structure specific analysis. For example, animals receiving a dose of 100 mg kg-1 p.o. showed a peak concentration of approximately 10 μM in the dialyzate. For comparison, tissue and plasma samples of the drug were measured under the same conditions using gas chromatography/mass spectrometry. This work demonstrates that the microdialysis technique in combination with the molecular specificity and high sensitivity of micro-electrospray tandem mass spectrometry can be used to study the time course of the appearance of unmodified drug in the brain of a single animal.",
keywords = "3- aminopropyl-n-butylphosphinic acid, CGP 36742, GABA antagonist, Mass spectrometry, Microdialysis, Pharmacokinetics",
author = "Andr{\'e}n, {Per E.} and Mark Emmett and DaGue, {Beverly B.} and Steulet, {Anne Fran{\cc}oise} and Peter Waldmeier and Caprioli, {Richard M.}",
year = "1998",
month = "3",
doi = "10.1002/(SICI)1096-9888(199803)33:3<281::AID-JMS631>3.0.CO;2-W",
language = "English (US)",
volume = "33",
pages = "281--287",
journal = "Biomedical and Environmental Mass Spectrometry",
issn = "1076-5174",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - Blood-brain barrier penetration of 3-aminopropyl-n-butylphosphinic acid (CGP 36742) in rat brain by microdialysis/mass spectrometry

AU - Andrén, Per E.

AU - Emmett, Mark

AU - DaGue, Beverly B.

AU - Steulet, Anne Françoise

AU - Waldmeier, Peter

AU - Caprioli, Richard M.

PY - 1998/3

Y1 - 1998/3

N2 - The detection and quantitation of the novel drug 3-aminopropyl-n- butylphosphinic acid (APBP), also known as CGP 36742, was performed in vivo using microdialysis and tandem mass spectrometry. This drug is a GABA-B antagonist with high specificity for GABA-B receptors. Animals received doses of 100, 200, 500 and 1000 mg kg-1 of the drug either intravenously or per os (p.o.). Microdialysis probes, placed by stereotaxis in either the frontal cortex or third ventricle of the rat, were used to collect dialyzate samples over several hours. Samples were then analyzed by micro-electrospray tandem mass spectrometry to achieve a molecular mass and structure specific analysis. For example, animals receiving a dose of 100 mg kg-1 p.o. showed a peak concentration of approximately 10 μM in the dialyzate. For comparison, tissue and plasma samples of the drug were measured under the same conditions using gas chromatography/mass spectrometry. This work demonstrates that the microdialysis technique in combination with the molecular specificity and high sensitivity of micro-electrospray tandem mass spectrometry can be used to study the time course of the appearance of unmodified drug in the brain of a single animal.

AB - The detection and quantitation of the novel drug 3-aminopropyl-n- butylphosphinic acid (APBP), also known as CGP 36742, was performed in vivo using microdialysis and tandem mass spectrometry. This drug is a GABA-B antagonist with high specificity for GABA-B receptors. Animals received doses of 100, 200, 500 and 1000 mg kg-1 of the drug either intravenously or per os (p.o.). Microdialysis probes, placed by stereotaxis in either the frontal cortex or third ventricle of the rat, were used to collect dialyzate samples over several hours. Samples were then analyzed by micro-electrospray tandem mass spectrometry to achieve a molecular mass and structure specific analysis. For example, animals receiving a dose of 100 mg kg-1 p.o. showed a peak concentration of approximately 10 μM in the dialyzate. For comparison, tissue and plasma samples of the drug were measured under the same conditions using gas chromatography/mass spectrometry. This work demonstrates that the microdialysis technique in combination with the molecular specificity and high sensitivity of micro-electrospray tandem mass spectrometry can be used to study the time course of the appearance of unmodified drug in the brain of a single animal.

KW - 3- aminopropyl-n-butylphosphinic acid

KW - CGP 36742

KW - GABA antagonist

KW - Mass spectrometry

KW - Microdialysis

KW - Pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=0031942214&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031942214&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1096-9888(199803)33:3<281::AID-JMS631>3.0.CO;2-W

DO - 10.1002/(SICI)1096-9888(199803)33:3<281::AID-JMS631>3.0.CO;2-W

M3 - Article

C2 - 9538527

AN - SCOPUS:0031942214

VL - 33

SP - 281

EP - 287

JO - Biomedical and Environmental Mass Spectrometry

JF - Biomedical and Environmental Mass Spectrometry

SN - 1076-5174

IS - 3

ER -