University of Tasmania
Browse

File(s) under permanent embargo

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

journal contribution
posted on 2023-05-16, 18:58 authored by Michael BreadmoreMichael Breadmore, Prochazova, A, Theurillat, R, Thormann, W
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.

History

Publication title

Journal of Chromatography A

Volume

1014

Issue

1-2

Pagination

57-70

ISSN

0021-9673

Department/School

School of Natural Sciences

Publisher

Elsevier

Place of publication

Amsterdam

Rights statement

The definitive version is available at http://www.sciencedirect.com

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the chemical sciences

Usage metrics

    University Of Tasmania

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC