Direct high‐performance liquid chromatographic separation of penbutolol enantiomers on a cellulose tris‐3,5‐dimethylphenyl carbamate chiral stationary phase

Penbutolol is a β‐adrenoceptor blocking agent, and it contains the clinically relevant (−)‐S‐enantiomer. It was reported that the (+)‐R‐enantiomer of penbutolol is pharmacologically 50 times less active than the (−)‐S‐isomer in β‐sympatholysis and without intrinsic sympathomimetic activity and refractory period in the heart muscle. Furthermore, the (+)‐R‐enantiomer does possess mutagenic activity. A high‐performance liquid chromatographic (HPLC) method is described for direct identification, stereochemical separation, and quantitation of (+)‐R‐enantiomer in the clinically used (−)‐S‐isomer. The method involves the use of cellulose tris‐3,5‐dimethylphenyl carbamate chiral stationary phase coated on silica gel (OD‐Chiralcel column). The capacity factors ( k ′) for the first eluted enantiomer and stereochemical separation factor (α) obtained were 1.32 and 1.98, respectively. The maximum stereochemical resolution factor ( R ) was 5.05. The method could be applied for optical purity determination of (−)‐(S)‐penbutolol in pharmaceutical formulation to detect for the presence of the undesirable (+)‐R‐enantiomer.