High-performance liquid chromatography of a new 2-amino-2-oxazoline: application to pharmacokinetic studies in dogs.
5-(1'-Phenyl-4'-piperazinomethyl)-2-amino-2-oxazoline (1; COR3224), a derivative of 2-amino-2-oxazolines with antidepressant properties in rats, was assayed in plasma by high-performance liquid chromatography. After back extraction, 1 and a ortho-O-methyl derivative of 1 as the internal standard were separated by reversed-phase liquid chromatography and measured by UV detection (235 nm). The method is rapid and specific: the detection was linear in the range 125-1000 micrograms.L-1, with a detection limit of 50 micrograms.L-1. This method allowed the determination of pharmacokinetic parameters in six beagle dogs after intravenous and oral administration of 14C-labeled 1 ([14C]1) in a crossover study. The comparison of the results obtained from total radioactivity counting and unchanged product evaluated by HPLC-UV suggest the presence of metabolites.
Laboratoire de Pharmacologie et de Pharmacocinétique, Faculté de Pharmacie, Chatenay-Malabry, France.
M I
MI
Damaj
J H
JH
Trouvin
B
B
Lambrey
C
C
Jacquot
D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D008297:Male; D010080:Oxazoles / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet
D000928:Antidepressive Agents; D007202:Indicators and Reagents; D010080:Oxazoles; C056984:COR 32-24