Evaluation of chiral purity for a substituted imidazole p38 MAP kinase inhibitor and its intermediates using a single chiral capillary electrophoresis method

被引:10
作者
Zhou, LL [1 ]
Thompson, R [1 ]
Ellison, D [1 ]
Wyvraft, JM [1 ]
机构
[1] Merck & Co Inc, Merck Res Labs, Rahway, NJ 07065 USA
关键词
capillary electrophoresis; chiral separation; cyclodextrins;
D O I
10.1002/elps.200405935
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The chiral separation of a substituted imidazole p38 MAP kinase inhibitor and its intermediates was investigated using capillary electrophoresis (CE) with various sulfated cyclodextrins. After initial screens, a single CE chiral method with a randomly sulfated beta-CD was selected for the evaluation of chiral purity for all three compounds. Operational parameters, such as the concentration of the chiral selectors, background electrolyte (or mobile phase) pH, organic modifiers, and temperature were varied in order to achieve an optimized method. The optimal method was validated in terms of linearity, sensitivity, precision, ruggedness, and specificity.
引用
收藏
页码:2860 / 2865
页数:6
相关论文
共 16 条
[1]   Overview of the status and applications of capillary electrophoresis to the analysis of small molecules [J].
Altria, KD ;
Elder, D .
JOURNAL OF CHROMATOGRAPHY A, 2004, 1023 (01) :1-14
[2]   Enantioseparations in capillary electromigration techniques: recent developments and future trends [J].
Chankvetadze, B ;
Blaschke, G .
JOURNAL OF CHROMATOGRAPHY A, 2001, 906 (1-2) :309-363
[3]  
Dorsey JG, 1998, ANAL CHEM, V70, p591R
[5]   Comprehensive strategy for chiral separations using sulfated cyclodextrins in capillary electrophoresis [J].
Evans, CE ;
Stalcup, AM .
CHIRALITY, 2003, 15 (08) :709-723
[6]   Enantioselective determination by capillary electrophoresis with cyclodextrins as chiral selectors [J].
Fanali, S .
JOURNAL OF CHROMATOGRAPHY A, 2000, 875 (1-2) :89-122
[7]   OPTIMIZATION OF THE SEPARATION OF ENANTIOMERS OF BASIC DRUGS - RETENTION MECHANISMS AND DYNAMIC MODIFICATION OF THE CHIRAL BONDING PROPERTIES ON AN ALPHA(1)-ACID GLYCOPROTEIN COLUMN [J].
HERMANSSON, J ;
GRAHN, A .
JOURNAL OF CHROMATOGRAPHY A, 1995, 694 (01) :57-69
[8]  
Murry JA, 2003, CURR OPIN DRUG DISC, V6, P945
[9]  
Okamoto Y, 1998, ANGEW CHEM INT EDIT, V37, P1020, DOI 10.1002/(SICI)1521-3773(19980504)37:8<1020::AID-ANIE1020>3.0.CO
[10]  
2-5