Dissociation Constants and Octanol-Water Partition Equilibria for Several Fluoroquinolones

The octanol/water partition and acid-base dissociation equilibria for a set of six fluoroquinolones have been studied by the shake-flask method at 25 degrees C and at 0.15 M NaCl ionic strength, determining the partition coefficient (logD) in the pH range 3 to 9. The substances studied are ciprofloxacin (CIP), danofloxacin (DAN), difloxacin (DIF), enrofloxacin (ENR), marbofloxacin (MAR), and sarafloxacin (SAR). After the partition equilibrium, the remaining fluoroquinolone concentration is determined in aqueous phase by liquid chromatography with fluorescence detection. The pK(a) values obtained are in accordance with the previously published data, ranging between 5.59 and 6.50 for pK(a1) and between 7.99 and 8.96 for pK(a2). The lipophilicity of the substances is low, with logK(OW) ranging between -1.09 to 0.68. Additionally, we have determined the octanol/water partition coefficient for the cationic species in all cases.