PGE-9509924

Postantibiotic effects (PAEs), postantibiotic sub-MIC effects, and sub-MIC effects of the new nonfluoroquinolone PGE-9509924, ciprofloxacin, and levofloxacin against gram-positive and gram-negative strains were investigated. In comparison to ciprofloxacin and levofloxacin, PGE-9509924 exerted very similar PAEs against all strains except for both strains of Streptococcus pneumoniae , where longer PAEs were found for PGE-9509924. All three investigated quinolones showed no minimal PAEs against Pseudomonas aeruginosa .

PGE-9509924 is a nonfluorinated quinolone and is active against a variety of susceptible and drug resistant bacteria in vitro and in animal infection models. A method for determining both enantiomers of PGE-9509924 in dog plasma has been developed. The enantiomers are derivatized with a chiral derivatizing agent, (-)-1-(9-fluorenyl)ethyl chloroformate (FLEC) and the resulting diastereomers are separated by reverse phase chromatography. Plasma samples are prepared via solid phase extraction (SPE) in a 96-well format prior to being derivatized. Samples are then analyzed by electrospray-LC/MS/MS with multiple reaction monitoring or by HPLC with fluorescence detection. Results of a side-by-side validation of the method with LC/MS/MS and HPLC/Fl detection are presented. Over the range selected for validation (0.025-10 micro g/ml), both methods give similar results with identical limits of quantitation. Due to the selectivity of LC/MS/MS and the use of a stable-isotopically labeled internal standard, significantly shorter chromatographic runtimes are achieved with LC/MS/MS, making it the method of choice for sample analysis.