Separation and quantitation of the four stereoisomers of itraconazole in pharmaceutical formulations by electrokinetic chromatography

被引:15
作者
Castro-Puyana, M [1 ]
Crego, AL [1 ]
Marina, ML [1 ]
机构
[1] Univ Alcala de Henares, Fac Quim, Dept Quim Analit, E-28871 Alcala De Henares, Madrid, Spain
关键词
antifungals; chiral separation; cyclodextrin; electrokinetic chromatography; itraconazole;
D O I
10.1002/elps.200500347
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The four stereoisomers of itraconazole were resolved for the first time by EKC using a CD as chiral selector. A study on the enantiomeric separation ability of different neutral CDs was carried out. Heptakis-2,3,6-tri-O-methyl-beta-CD was shown to provide the highest values for the enantiomeric resolution. The influence of some experimental conditions, such as pH, chiral selector concentration, and temperature, on the enantiomeric separation was also studied. The use of a 100 mM phosphate buffer (pH 2.5), 30 mM in heptakis-2,3,6-tri-O-methyl-beta-CD together with an applied voltage of 30 kV and a temperature of 20 degrees C enabled the separation of the enantiomers of itraconazole with high resolutions (R-s > 3.0). Finally, the method was validated and successfully applied to the quantitation of itraconazole in three pharmaceutical formulations.
引用
收藏
页码:887 / 895
页数:9
相关论文
共 51 条
[1]   APPROACHES TO OPTIMIZATION OF PRECISION IN CAPILLARY ELECTROPHORESIS [J].
ALTRIA, KD ;
FABRE, H .
CHROMATOGRAPHIA, 1995, 40 (5-6) :313-320
[2]   ESSENTIAL PEAK AREA NORMALIZATION FOR QUANTITATIVE IMPURITY CONTENT DETERMINATION BY CAPILLARY ELECTROPHORESIS [J].
ALTRIA, KD .
CHROMATOGRAPHIA, 1993, 35 (3-4) :177-182
[3]  
Amini A, 2001, ELECTROPHORESIS, V22, P3107, DOI 10.1002/1522-2683(200109)22:15<3107::AID-ELPS3107>3.0.CO
[4]  
2-Z
[5]   CHIRAL SEPARATION OF BASIC DRUGS BY CAPILLARY ZONE ELECTROPHORESIS WITH CYCLODEXTRIN ADDITIVES [J].
BECHET, I ;
PAQUES, P ;
FILLET, M ;
HUBERT, P ;
CROMMEN, J .
ELECTROPHORESIS, 1994, 15 (06) :818-823
[6]  
BECKSAGUE CM, 1993, J INFECT DIS, V167, P1247, DOI 10.1093/infdis/167.5.1247
[7]   Enantiomer separation of drugs by capillary electromigration techniques [J].
Blaschke, G ;
Chankvetadze, B .
JOURNAL OF CHROMATOGRAPHY A, 2000, 875 (1-2) :3-25
[8]   Determination of itraconazole and hydroxyitraconazole in human serum and plasma by micellar electrokinetic chromatography [J].
Breadmore, MC ;
Procházková, A ;
Theurillat, R ;
Thormann, W .
JOURNAL OF CHROMATOGRAPHY A, 2003, 1014 (1-2) :57-70
[9]   Capillary electrophoresis evidence for the stereoselective metabolism of itraconazole in man [J].
Breadmore, MC ;
Thormann, W .
ELECTROPHORESIS, 2003, 24 (15) :2588-2597
[10]   Enantiomeric separation of ketoconazole and terconazole antifungals by electrokinetic chromatography: Rapid quantitative analysis of ketoconazole in pharmaceutical formulations [J].
Castro-Puyana, M ;
Crego, AL ;
Marina, ML .
ELECTROPHORESIS, 2005, 26 (20) :3960-3968