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 w hich contain a substituted pipecolinic amide were developed. After pre liminary screening, a representative of this series, compound BILA 218 5 BS, demonstrated an IC50 value of 3.3 nM in the enzymatic assay and an EC(50) value of 2.0 nM in cell culture. The plasma profile and bioa vailability 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 l iquid 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 B S was 6-12 nM.