QUANTIFICATION OF THE INDIVIDUAL ENANTIOMER PLASMA-CONCENTRATIONS OF THE CANDIDATE ANTIMALARIAL AGENT ROMETHYL)PHENOXY]-8-QUINOLINYL]-1,4-PENTANEDIAMINE (WR-238,605)

A high-performance liquid chromatographic method was developed to quan titate the plasma concentrations of the individual enantiomers of a ca ndidate 8-aminoquinoline antimalarial agent WR 238,605 (I). The method employed one-step liquid extraction of a 0.5-ml plasma sample followe d by direct injection of the extract through a chiral column and detec tion by fluorescence. Quantification was achieved using an internal st andard. The limit of quantification was 10 ng/ml for each enantiomer. The method is sufficiently sensitive to quantitate the plasma concentr ations of both enantiomers for 30 days following a single oral dose of 400 mg of the antimalarial agent administered as the racemic succinat e salt to healthy human male volunteers. In nearly all samples taken 1 2 h to 30 days post-dose from three subjects, the difference in the pl asma concentrations of the two enantiomers is less than 10%.