Enantiomeric resolution of doxazosin mesylate and its process-related substances on polysaccharide chiral stationary phases.
Enantiomeric resolution of doxazosin mesylate and its process-related substances on polysaccharide chiral stationary phases.
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DOI：
10.1016/j.jpba.2006.01.019
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发表时间：
2006-06
影响因子：
3.4
通讯作者：
R. Nageswara Rao;D. Nagaraju;A. Narasa Raju
中科院分区：
文献类型：
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作者：
R. Nageswara Rao;D. Nagaraju;A. Narasa Raju
建立了在多糖固定相直链淀粉三-（3,5-二甲基苯基氨基甲酸酯）（Chiralpak AD-H）和纤维素三-（3,5-二甲基苯基氨基甲酸酯）（Chiralcel OD-H）上分离消旋型甲磺酸多沙唑嗪及其合成前体的高效液相色谱方法。以不同比例的正己烷-醇- 0.1%二乙胺（乙醇、1-丙醇和2-丙醇）为流动相，以Rs bbb1.50进行了基线分离。研究了醇类改性剂浓度对分辨率的影响。直链淀粉基Chiralpak AD-H柱与纤维素基Chiralcel OD-H柱的分离效果较好。考察了溶质和溶剂的结构特征对对映体区分的影响。采用紫外检测器在240nm处检测，串联极化检测器进行鉴定。该方法不仅适用于甲磺酸多沙唑嗪的工艺开发，也适用于原料药和药品对映体纯度的测定。
High-performance liquid chromatographic methods for separation of racemic doxazosin mesylate and its synthetic precursors on polysaccharide based stationary phases viz., amylose tris-(3,5-dimethylphenylcarbamate) (Chiralpak AD-H) and cellulose tris-(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) were developed. The base line separation with Rs>1.50 was obtained using a mobile phase containing n-hexane–alcohol–0.1% diethylamine (ethanol, 1-propanol and 2-propanol) in various proportions. The effect of concentration of the alcoholic modifiers on the resolution was studied. A good separation was achieved on amylose based Chiralpak AD-H column when compared with cellulose based Chiralcel OD-H. The effects of structural features of the solutes and solvents on discrimination between the enantiomers were examined. The detection was carried out at 240nm with UV detector while identification by polarimetric detector connected in series. The method was suitable not only for process development of doxazosin mesylate but also determination of enantiomeric purity of bulk drugs and pharmaceuticals.