[Chiral separation and preparation of three new antagonists of alpha 1-adrenoceptors by chiral mobile phase HPLC].
OBJECTIVE
To establish new methods for the chiral separation and preparation of three new drugs, alfuzosin, terazosin and doxazosin.


METHODS
By optimizing factors which affect the chiral separation, modifier of solvent, chiral additive, pH of mobile phase, modifier of organic base and stationary phase, the optimum condition for chiral separation were selected. The preparation of enantiomers was carried out on semi-preparative reverse phase column (7.8 mm x 250 mm C4 5 microns). Acetonitrile-water modified by the addition of carboxymethyl-beta-cyclodextrin (2%-5%, w/v) was applied as chiral mobile phase.


RESULTS
The enantiomers of three new drugs were base-line-separated and milligram-scale samples of enantiomer were obtained.


CONCLUSIONS
The newly established method can be used in research and development of the enantiomers of three new drugs.
Niu
Chang-qun
CQ
Department of Pharmacology, School of Pharmacy, Hebei Medical University, Research and Development Drug Center, North China Pharmaceutical Corporation, Shijiazhuang, China. niuchangqun@yeal.net
Ren
Lei-ming
LM
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D017292:Doxazosin / Q000302:isolation & purification; D015394:Molecular Structure; D011224:Prazosin / Q000031:analogs & derivatives* / Q000302:isolation & purification; D011799:Quinazolines / Q000302:isolation & purification
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; C041226:Terazosin; C047638:alfuzosin; D017292:Doxazosin; D011224:Prazosin