REDUCTION OF IN-VITRO CLASTOGENICITY INDUCED BY THE MIXTURE OF OPTICAL ISOMERS OF NADIFLOXACIN DURING STORAGE

The fluoroquinolone antibacterial agent, nadifloxacin (NDFX, CAS 12485 8-35-1), is a racemic compound. The storage effect on the in vitro cla stogenicity of a solution of the racemic compound and a mixture soluti on of the optical isomers of NDFX, prepared by mixing equal amounts of S- and R-enantiomers, was investigated The potential of NDFX and the enantiomer mixture, prepared from equal amounts of each S- and R-enant iomer, to induce chromosomal aberrations in vitro was investigated in cultured fibroblasts derived from Chinese hamster lung cells immediate ly, 2 and 4 weeks after. preparation of the test solutions (stored at 20 degrees C, protected from light) using 24 h of continuous treatment method. In the results, NDFX did not significantly increase the incid ence of chromosomal aberrations at 200 mu g/ml regardless of the stora ge period. On the other hand the mixture significantly increased the i ncidence of chromosomal aberrations at 200 mu g/ml immediately after p reparation to an extent similar to that of S-enantiomer alone, but the mixture did not do so after 2 curd 4 weeks of storage, Neither S- nor R-enantiomer changed the chromosomal aberration inducibility during s torage. The content and optical purity of the test substances in each test solution also did not change during storage. These facts suggeste d that the molecular conditions of each optical isomer in the mixture solution became equivalent to that in the racemic solution during stor age periods.