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.
A chromatographic-densitometric method has been established for identification and quantitation of selected beta-adrenergic-blocking agents in pharmaceutical preparations. Retention factors,
, and characteristic absorption spectra of 11 drugs chromatographed on silica gel 60 F
HPTLC plates with six mobile phases were used for identification. Quantitation and validation of the method was performed for atenolol, acebutolol, propranolol, and bisoprolol using chloroform-methanol-ammonia, 15 + 7 + 0.2 (
), as mobile phase. UV densitometric measurements were performed at the wavelength of maximum absorption. Pharmaceutical preparations used in medicine and from a variety of manufacturers were analyzed and the method shown to be sufficiently sensitive for analysis of these samples. The limits of detection and determination ranged from 30 to 400 ng and recovery was from 97.14 to 102.18%. The precision of the method, described by the equation
, is good and the range of linearity is wide — from 0.020 to 0.250% for individual constituents.
An isothermal titration calorimetry (ITC) method
to measure the heat effects evolving from the binding between cation exchanger
Amberlite IRP 69 and the cationic drug substances propranolol hydrochloride
(PROP), metoprolol tartarate (METO), acebutolol hydrochloride (ACEB) and chlorpheniramine
maleate (CPR) has been developed. The method gives repeatable results with
an error about 5% for the beta-blockers PROP, METO and ACEB, and about 10%
for the antihistamine CPR.
The calculation of the thermodynamic parameters enthalpy
and Gibbs free energy change (ΔGbind)
show significant differences between the different drug substances.
blockers. In combination with other drugs (diuretics, betablockers, …) it is used to treat cardiovascular diseases: hypertension, angina pectoris, etc [ 14 ]. On the market, this drug is quite common, most often in the form of tablets in doses of 5 mg and