Resolution of racemic metoprolol, propranolol, carvedilol, bisoprolol, salbutamol, and labetalol, commonly used β-blockers, into their enantiomers has been achieved by TLC on silica gel plates impregnated with optically pure L
-Glu and L
-Asp. Acetonitrile-methanol-water-dichloromethane and acetonitrile-methanol-water-glacial acetic acid mobile phases in different proportions enabled successful separation. The spots were detected with iodine vapor. The detection limits were 0.23, 0.1, 0.27, 0.25, 0.2, and 0.2 μg for each enantiomer of metoprolol, propranolol, carvedilol, bisoprolol, salbutamol, and labetalol, respectively.
A simple and rapid method has been established for indirect separation of the enantiomers of (R,S)-metoprolol and (R,S)-carvedilol by reversed-phase TLC. Beta blockers derivatized with 1-fluoro-2,4-dinitrophenyl-5-l-alanine amide (Marfey’s reagent, FDNP-l-Ala-NH2) and its six structural variants (FDNP-l-Phe-NH2, FDNP-l-Val-NH2, FDNP-l-Pro-NH2, FDNP-l-Leu-NH2, FDNP-l-Met-NH2, and FDNP-d-Phg-NH2) were spotted on precoated plates. (R,S)- Metoprolol and (R,S)-carvedilol were isolated from pharmaceutical dosage forms and purified. The diastereomers were separated most effectively by use of mobile phases containing acetonitrile and triethylamine-phosphate buffer (50 mM, pH 5.5). The results obtained by use of Marfey’s reagent were compared with those obtained by use of the other variants. The effects of buffer concentration, pH, and concentration of organic modifier were studied.
Resolution of the enantiomers of racemic atenolol, metoprolol, propranolol, and labetalol, commonly used β-blockers, has been achieved by TLC on silica gel plates using vancomycin as chiral impregnating reagent or as chiral mobile phase additive. With vancomycin as impregnating agent, successful resolution of the enantiomers of atenolol, metoprolol, propranolol, and labetalol was achieved by use of the mobile phases acetonitrile-methanol-water-dichloromethane 7:1:1:1 (
), acetonitrile-methanol-water 6:1:1 (
), acetonitrile-methanol-water-dichloromethane-glacial acetic acid 7:1:1:1:0.5 (
), and acetonitrile-methanol-water 15:1:1 (
), respectively. With vancomycin as mobile phase additive, successful resolution of the enantiomers of metoprolol, propranolol, and labetalol was achieved by use of the mobile phases acetonitrile-methanol-0.56 mM aqueous vancomycin (pH 5.5) 6:1:1 (
), acetonitrile-methanol-0.56 mM aqueous vancomycin (pH 5.5) 15:1:2 (
), and acetonitrile-methanol-0.56 mM aqueous vancomycin (pH 5.5)-dichloromethane 9:1:1.5:1 (
), respectively. Spots were detected by use of iodine vapor. The detection limits were 1.3, 1.2, 1.5, and 1.4 μg for each enantiomer of atenolol, metoprolol, propranolol, and labetalol, respectively.
Authors:Ravi Bhushan, Jürgen Martens, Charu Agarwal, and Shuchi Dixit
Cu(II) complexes of L-threonine, L-serine, and L-tartaric acid were prepared and used as ligand exchange reagents for enantiomeric resolution of some of the β-blockers (bisoprolol, metoprolol, and propranolol) and a β2-agonist (salbutamol). Impregnated thin-layer plates were prepared by spreading slurry of silica gel prepared in the solutions of each of the three ligand exchange reagents. The spots were detected with iodine. Effect of temperature on enantioresolution was also studied. The detection limits were found in the range 0.19–0.26 μg for each enantiomer. L-Ser proved to be a good ligand using a common mobile phase in each case.