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

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

Research output: Contribution to journalArticle

28 Scopus citations


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
Issue number3
StatePublished - Mar 1 1998



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

ASJC Scopus subject areas

  • Spectroscopy

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