Role of chemical structure in stereoselective recognition of beta-blockers by cyclodextrins in capillary zone electrophoresis.

Author(s): Gagyi L, Gyeresi A, Kilar F

Affiliation(s): University of Medicine and Pharmacy Targu-Mures, Institute of Pharmaceutical Chemistry, Str. Gheorghe Marinescu nr. 38, 540139 Targu-Mures, Romania.

Publication date & source: 2008-04-24, J Biochem Biophys Methods., 70(6):1268-75. Epub 2007 Oct 13.

Publication type:

Most of the beta-blocking drugs for treating diseases of the cardiovascular system are chiral aryloxy-propanolamine derivatives. Tipically, the S(-) enantiomers are more active than the R(+) enantiomers. Only some of them (for example timolol) are used as single enantiomers, the others are employed as racemates. For the determination of the enantiomeric purity of timolol European Pharmacopoeia prescribes an HPLC method using chiral stationary phase. However, the use of chiral capillary zone electrophoresis for the determination of the enantiomeric purity is of pharmaceutical interest. This study describes the application of various cyclodextrin derivatives, hydroxypropyl-beta-cyclodextrin, randomly methylated beta-cyclodextrin, sulphated beta-cyclodextrin and sulphated alpha-cyclodextrin for the stereoselective analyses of beta-blockers. Baseline separation was obtained for bopindolol, carvedilol, mepindolol, pindolol and alprenolol, while only partial separation was observed for sotalol, propranolol, oxprenolol, atenolol, bisoprolol, bupranolol, and metoprolol. The uneven molecular recognition of the enantiomers of the beta-blockers, especially of the optical isomers of labetalol and nadolol, showed the importance of the chemical nature of the separators and the analytes.