Analytical and Bioanalytical Chemistry

, Volume 404, Issue 1, pp 217–228 | Cite as

Simultaneous determination of triazole antifungal drugs in human plasma by sweeping-micellar electrokinetic chromatography

  • Shu-Chiao Lin
  • Hsiang-Yin Liu
  • Shu-Wen Lin
  • Ming Yao
  • Un-In Wu
  • Hsiu-Po Kuo
  • Ching-Hua Kuo
Original Paper
First Online:
Received:
Revised:
Accepted:

Abstract

The number of cases of invasive fungal infections (IFIs) has risen significantly in recent years; therefore, this study developed a sensitive and effective sweeping-micellar electrokinetic chromatography (MEKC) method for the simultaneous determination of the three most frequently used triazole antifungal drugs for the treatment of IFIs, which included voriconazole, itraconazole, and posaconazole. Due to the diverse lipophilicity of the tested drugs, the analytical conditions that resulted in good resolution between itraconazole and posaconazole caused the peak for voriconazole to split. The splitting phenomenon was resolved by incorporating a high-salt stacking mechanism into the sweeping-MEKC method. The optimum background electrolyte was composed of 25 mM phosphoric acid solution (pH 2.2), 100 mM sodium dodecyl sulfate, 13 % acetonitrile, and 13 % tetrahydrofuran. The best peak shape of voriconazole was obtained when the conductivity ratio between the sample matrix and background electrolyte was 2.3. Compared to the conventional MEKC mode, the enhancement factor of the sweeping-MEKC method was 66 for itraconazole, 55 for posaconazole, and 43 for voriconazole. The sweeping-MEKC method was validated in terms of precision, accuracy, linearity, specificity, selectivity, and sensitivity. The linearity ranges of the method covered the commonly used therapeutic ranges of the three drugs. The developed sweeping-MEKC method was successfully applied to the analysis of clinical samples, thus demonstrating its applicability for clinical use.

Fig

 

Keywords

Itraconazole Voriconazole Posaconazole Sweeping-MEKC High salt stacking Therapeutic drug monitoring 

Abbreviations

ACN

Acetonitrile

BGE

Background electrolyte

CE

Capillary electrophoresis

EtOH

Ethanol

HPLC-MS/MS

High-performance liquid chromatography coupled with tandem mass spectrometry

IFI

Invasive fungal infection

LOD

Limit of detection

LOQ

limit of quantification

MEKC

Micellar electrokinetic chromatography

MeOH

Methanol

NaOH

Sodium hydroxide

RSD

Relative standard deviation

SDS

Sodium dodecyl sulfate

SPE

Solid-phase extraction

THF

Tetrahydrofuran

UV–vis

Ultraviolet–visible

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Notes

Acknowledgments

This study was supported by the National Science Council of Taiwan (NSC 99-2320-B-002-013-MY3). The authors thank the NTU Integrated Core Facility for Functional Genomics of National Research Program for Genomic Medicine of Taiwan for technical assistance.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Shu-Chiao Lin
    • 1
    • 2
  • Hsiang-Yin Liu
    • 1
  • Shu-Wen Lin
    • 1
    • 2
    • 3
  • Ming Yao
    • 4
  • Un-In Wu
    • 5
  • Hsiu-Po Kuo
    • 6
  • Ching-Hua Kuo
    • 1
    • 2
  1. 1.School of Pharmacy, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  2. 2.Department of PharmacyNational Taiwan University HospitalTaipeiTaiwan
  3. 3.Graduate Institute of Clinical Pharmacy, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  4. 4.Division of Hematology, Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
  5. 5.Division of Infectious Diseases, Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
  6. 6.Department of Chemical and Materials EngineeringChang Gung UniversityTao-YuanTaiwan

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