Simultaneous determination of vigabatrin and amino acid neurotransmitters in brain microdialysates by capillary electrophoresis with laser-induced fluorescence detection.
Capillary electrophoresis with laser-induced fluorescence detection (CE-LIFD) coupled to in vivo microdialysis sampling was used in order to monitor simultaneously a drug and several neurotransmitters in the brain extracellular fluid. Determination of the antiepileptic drug vigabatrin and the amino acid neurotransmitters glutamate (Glu), l-aspartate (l-Asp) and gamma-aminobutyric acid (GABA) was performed on low-concentration samples which were derivatized with naphthalene-2,3-dicarboxaldehyde (NDA) and separated using a pH 9.2 75 mM sodium borate running buffer containing 60 mM sodium dodecyl sulfate (SDS) and 5mM hydroxypropyl-beta-cyclodextrin (HP-beta-CD). Glu, l-Asp and vigabatrin derivatized at a concentration of 1.0 x 10(-9) M, and GABA derivatized at a concentration of 5.0 x 10(-9) M, produced peaks with signal-to-noise ratios of 8:1, 8:1, 4:1 and 5:1, respectively. The nature of the neurotransmitter peaks found in rat brain microdialysates was confirmed by both electrophoretic and pharmacological validations. This method was used for monitoring vigabatrin and amino acid neurotransmitters in microdialysates from the rat striatum during intracerebral infusion of the drug and revealed rapid vigabatrin-induced changes in GABA and Glu levels. This original application of CE-LIFD coupled to microdialysis represents a powerful tool for pharmacokinetic/pharmacodynamic investigations.
Benturquia
Nadia
N
Laboratoire de Neuropharmacologie et Neurochimie, INSERM U512, Faculté de Pharmacie, et Institut Fédératif des Neurosciences de Lyon, IFR 19, Université Claude Bernard, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France.
Parrot
Sandrine
S
Sauvinet
Valérie
V
Renaud
Bernard
B
Denoroy
Luc
L
D000596:Amino Acids / Q000032:analysis*; D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D007834:Lasers; D008297:Male; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence / Q000379:methods*; D020888:Vigabatrin / Q000032:analysis*
D000596:Amino Acids; D018377:Neurotransmitter Agents; D020888:Vigabatrin