Development and Validation of a LC Method for the Enantiomeric Purity Determination of S-Mirabegron in a Pharmaceutical Drug Substance Using a Amylose Immobilised Based Chiral Stationary Phase

A Chiral liquid chromatographic (LC) method was developed for the enantiomeric resolution of Mirabegron(R)-2-(2-aminothiazol-4-yl)-N-(4-(2-(2-hydroxy-2-phenyl ethyl) amino) ethyl) Phenyl acetamide, adrenoceptor agonist bulk drugs. The enantiomers of mirabegron were resolved on a Chiralpak IF (250mm x 4.6mm, 3.0µm) column using a mobile phase system containing n-Heptane, methyl tertiary butyl ether, methanol and ethanol amine in the ratio of (30:28:42:0.1v/v/v/v). The resolution between the enantiomers was found not less than 4.0.  The presence of methyl tertiary butyl ether and ethanol amine in the mobile phase has played an important role in enhancing chromatographic efficiency and resolution between the enantiomers. The developed method was extensively validated and proved to be robust.  The limit of detection and limit of quantification of (S) enantiomer were found to be 0.2µgmL-1 and 0.6 µgmL-1 respectively for 15µl injection volume. The percentage recovery of (S) enantiomer was ranged from 98.5 to 102.5 in bulk drug samples of mirabegron. Mirabegron sample solution and mobile phase were found to be stable for at least 48hrs. The proposed method was found to be suitable and accurate for the quantitative determination of (S)-enantiomer in bulk drugs.