Indirect resolution of beta-blocker agents by reversed-phase capillary electrochromatography.
The indirect resolution of five beta-adrenoreceptor blocking agents (propranolol, oxprenolol, pindolol, metoprolol, and atenolol) using precolumn derivatization with (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC), and capillary electrochromatography (CEC) is reported. Three octadecylsilanized (ODS) silica gel-based stationary phases, differing in particle diameter and carbon surface density for suitability of determination of the enantiomeric composition of these substances in drugs and biological fluids, were studied. Under optimum separation conditions, all the investigated compounds were baseline-resolved within acceptable analysis times (i.e., between 10-16 min). The resolution values ranged between 1.80 and 1.14, and the separation factors were in no case less than 1.07. The possible use of the developed CEC method for the determination of enantiomeric composition of beta-adrenoreceptor blocking agents in drug substances was investigated. A study, in which the enantiomers of metoprolol were examined regarding specificity, reproducibility, limit of detection, and ruggedness, was developed in accordance with some analytical procedures for method validation.
Istituto di Metodologie Chimiche, CNR-Area della Ricerca di Roma1, Rome, Italy. zeineb.aturki@imc.cnr.it
Zeineb
Z
Aturki
Francesca
F
Vichi
Antonella
A
Messina
Massimo
M
Sinibaldi
D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000302:isolation & purification*; D000605:Amino Alcohols / Q000737:chemistry; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods*; D005449:Fluorenes / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D011433:Propranolol / Q000302:isolation & purification; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D000605:Amino Alcohols; D002021:Buffers; D005449:Fluorenes; C052812:1-(9-fluorenyl)ethyl chloroformate; D011433:Propranolol