SEMIPREPARATIVE CHROMATOGRAPHIC PURIFICATION OF THE ENANTIOMERS S-(-)-AMLODIPINE AND R-(-AMLODIPINE())

Pharmacokinetic studies of optically pure compounds after single enant iomer administration are becoming increasingly important. The process of racemization in vivo can diminish all expected advantages of single enantiomer treatment. Amlodipine, one of the calcium channel blockers , currently used in therapy as a racemate, is one of such drugs under study. In order to administer single enantiomers of amlodipine to heal thy volunteers both were chromatographically purified and characterise d. The two optical isomers of amlodipine, active S-(-)- and non-active R-(+)-amlodipine, were purified using chromatographic procedure adopt ed from the analytical separation. Enantiomers were successfully conve rted to benzenesulphonic salt without any racemization. All semi-prepa rative purifications were monitored with complementary analytical meth ods, HPLC and CE, along with the determination of optical activity so that the final product was sufficiently defined for further in vivo st udies. The analytical method developed for the determination of plasma concentrations of each enantiomer of amlodipine in these studies is a lso briefly described.