Racemic metoprolol is a selective ß1-blocker, which is used in cardiovascular disease treatment. It has been found that (S)-metoprolol has a higher affinity to bind the ß-adrenergic receptor compared to (R)-metoprolol. Moreover, the regulatory authorities’ high market demand and guidelines have increased the preference for single enantiomer drugs. In this work, the lipase-catalyzed kinetic resolution of racemic metoprolol was performed to obtain the desired enantiomer. The type of lipase, acyl donor, and solvent were screened out. This was achieved by Candida antarctica B lipase-catalyzed transesterification of racemic metoprolol in hexane and vinyl acetate as the solvent and an acyl donor, which gave maximum conversion of (S)-metoprolol (XS) of 52%, enantiomeric excess of substrate, (ees) of 92% and product (eeP) of 90% with enantiomeric ratio (E) of 62. This method can be considered as green chemistry, which can be applied to produce other enantiopure beta-blockers.
Enantiomeric separation of the racemic metoprolol was investigated using a reverse phase HPLC (RP-HPLC) with Methyl-beta-cyclodextrin (M-B-CD) as chiral mobile phase additive. A comparison of the enantioseparation of the racemic metoprolol, the system suitability, linearity, accuracy, limit of detection and quantification was undertaken to show the performance between two C18 columns, a Zorbax Eclipse XDB C-18 column (15 cm x 10 mm, 10 μm) and a Syncronis C18 HPLC column (250 mm x 4.6 mm, 5.0 μm) using high performance liquid chromatography with the same condition of mobile phase composition, pH value of the mobile phase and concentration of chiral additives. The resolution was achieved using a mobile phase consisting of a mixture of aqueous solution (3.5 g M-ß-CD in 300 ml H20), methanol with a volumetric ratio of 86:14 (v/v) and a flow rate of 1.0 ml/min and 0.5 ml/min for the columns respectively. Conversion of S-metoprolol found in this study are 60%, 51%, 15%.
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