Determination of the HIV protease inhibitor BILA 2185 BS in rat plasma by liquid-liquid extraction and high performance liquid chromatography photodiode array detector.
A novel series of hydroxyethylamine-based inhibitors of HIV protease which contain a substituted pipecolinic amide were developed. After preliminary screening, a representative of this series, compound BILA 2185 BS, demonstrated an IC50 value of 3.3 nM in the enzymatic assay and an EC50 value of 2.0 nM in cell culture. The plasma profile and bioavailability values for BILA 2185 BS in the rat will be presented. The analyte was isolated from rat plasma using a liquid-liquid extraction procedure. The analytical technique used utilizes a high performance liquid chromatography system with photodiode array detector. The range of the standard curve was from 10 to 5000 nM. Recovery values averaged 72.4 +/- 8.6% (mean +/- S.D.). The limit of detection for BILA 2185 BS was 6-12 nM.
Liard
F
F
Department of Pharmacology, Bio-Méga/Boehringer Ingelheim Research Inc., Laval, Québec, Canada.
Ghiro
E
E
Paris
W
W
Yoakim
C
C
D000818:Animals; D001682:Biological Availability; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D017320:HIV Protease Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D007202:Indicators and Reagents; D008297:Male; D011725:Pyridines / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards
C102403:BILA 2185 BS; D017320:HIV Protease Inhibitors; D007202:Indicators and Reagents; D011725:Pyridines