Determination of BMS-284756, a new quinolone, in mouse serum by high-performance liquid chromatography with fluorescence detection

A sensitive, simple, and accurate method for determination of BMS-284756, a novel des-F(6)-quinolone antimicrobial agent in mouse serum was developed by HPLC with fluorescence detection. Sample preparations were carried out b y protein precipitation with the addition of acetonitrile, followed by evap oration of the acetonitrile to dryness. The resultant residual was then rec onstituted in 0.01 M HCl and injected onto a Nucleosil 100 10 mum, C-18 25 cmX4.6 mm analytical column. The mobile phase consisted of acetonitrile-0.0 1 M NaH2PO4 (20:80, v/v) with 0.01 M tetrabutylammonium hydrogen sulfate. T he fluorescence of the column effluent was monitored at an excitation wavel ength of 290 nm and an emission wavelength of 418 rim. The assay was shown to be linear from 0.2 to 10.0 mug/ml (R-2=0.998). Mean recovery was determi ned as 95.1%. Inter- and intra-assay precisions were <6% RSD. The HPLC meth od developed has been applied to determine the pharmacokinetics of BMS-2847 56 in a murine bacterial infection model. (C) 2001 Elsevier Science B.V. Al l rights reserved.