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Determination of itraconazole and hydroxyitraconazole in human serum and plasma by micellar electrokinetic chromatography

Citation

Breadmore, MC and Prochazova, A and Theurillat, R and Thormann, W, Determination of itraconazole and hydroxyitraconazole in human serum and plasma by micellar electrokinetic chromatography, Journal of Chromatography A, 1014, (1-2) pp. 57-70. ISSN 0021-9673 (2003) [Refereed Article]


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DOI: doi:10.1016/S0021-9673(03)00573-9

Abstract

The electrokinetic separation of the hydrophobic antimycotic drug itraconazole (ITC) and its major metabolite, hydroxyitraconazole (HITC), by a binary aqueous–organic solvent medium containing sodium dodecylsulfate, by microemulsion electrokinetic chromatography (MEEKC) and by micellar electrokinetic chromatography (MEKC) was studied. The results suggest that the first approach is difficult to apply and that there is no substantial difference between separations performed using MEEKC and MEKC modified with n-butanol. The simpler MEKC method is more than adequate and was thus employed for the analysis of ITC and HITC in human serum and plasma. Separation was achieved in plain fused-silica capillaries having a low-pH buffer (pH 2.2) with sodium dodecyl sulfate micelles and reversed polarity. The addition of 2-propanol and n-butanol enhanced analyte solubility and altered the selectivity of the separation by influencing the magnitude of the electrophoretic component in the separation mechanism. Under optimised conditions and using head-column field-amplified sample stacking, an internal standard, ITC and two forms of HITC could be separated in under 9 min, with detection limits less than 0.01 ìg/mL. Analysis of samples from patients currently prescribed ITC revealed a different HITC peak area ratio to that of the standards, suggesting a stereoselective component of ITC metabolisation. Comparison of MEKC data with those of a HPLC method employed on a routine basis showed excellent agreement, indicating the potential of this approach for therapeutic drug monitoring of ITC.

Item Details

Item Type:Refereed Article
Keywords:Itraconazole; Hydroxyitraconazole; Microemulsion electrokinetic chromatography; Electrokinetic chromatography
Research Division:Chemical Sciences
Research Group:Analytical Chemistry
Research Field:Separation Science
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Chemical Sciences
Author:Breadmore, MC (Professor Michael Breadmore)
ID Code:43546
Year Published:2003
Web of Science® Times Cited:26
Deposited By:Chemistry
Deposited On:2007-03-15
Last Modified:2010-03-16
Downloads:1 View Download Statistics

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