Applied chiral phase liquid chromatography in enantiomeric separation of cardiovascular drugs

Abstract

The majority of frequently prescribed therapeutic agents are formulated and commercialized in the racemic form, even though, for some of them, it has already been demonstrated that the pharmacological and/or toxicological effects are associated only with one of the enantiomers. Moreover, it is well known that these antipodes can present different pharmacokinetic and pharmacodynamic profiles. In this work we selected drugs that belong to an important group of pharmaceuticals, frequently prescribed in the treatment of cardiovascular disorders. The direct enantiomeric separations of atenolol, betaxolol, metoprolol and nadolol were obtained using the chiral stationary phase cellulose tris-3,5-dimethylphenyl-carbamate, Chiralcel OD® (250 x 4,6 mm, 10 µm). The enantiomers of pindolol were separated with the chiral stationary phase derived from dinitro-benzoyl (DNB) (S, S) alpha-Burke 2® (250x4.6 mm, 10 µm). The drugs were chromatographed at room temperature, with injection volumes of 20 µL. The detention was made at 276 nm except for pindolol, which was detected at 220 nm. The proposed methods in this work using HPLC-CSP offer advantages over contemporaneous techniques of enantiomeric separation, being rapid and efficient, and can be used in the simultaneous quantitative analysis of referred enantiomers in pharmaceutical preparations and biological samples.