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Simultaneous determination of voriconazole, posaconazole, itraconazole and hydroxy-itraconazole in human plasma using

Nicole Jenkins1, Marion Black1, Hans G Schneider2

  • 1Clinical Biochemistry Unit, Alfred Pathology Service, Melbourne, Australia.

Clinical Biochemistry
|January 13, 2018
PubMed
Abstract

Insights

A new LC-MS/MS method accurately measures voriconazole, posaconazole, and itraconazole in plasma. This rapid and sensitive assay is suitable for high-throughput clinical laboratories managing invasive fungal infections.

Area of Science:

  • Analytical Chemistry
  • Clinical Chemistry
  • Pharmacology

Background:

  • Invasive fungal infections (IFIs) pose a significant threat to immunocompromised patients.
  • Triazole antifungals are crucial for IFI prevention and treatment.
  • Accurate therapeutic drug monitoring is essential for optimizing patient outcomes.

Purpose of the Study:

  • To develop and validate a sensitive, robust, and rapid LC-MS/MS method for simultaneous quantification of voriconazole, posaconazole, and itraconazole in human plasma.
  • To establish a method suitable for routine clinical use in high-risk patient populations.

Main Methods:

  • Plasma samples (50μL) underwent protein precipitation with deuterated internal standards.
  • Analysis was performed using Ultra Performance Liquid Chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS).
  • Chromatographic separation was achieved on a C18 column with a run time under 5 minutes.

Main Results:

  • The LC-MS/MS method demonstrated excellent precision (intra-assay CVs < 6.7%, inter-assay CVs < 8.3%).
  • The lower limit of quantification for all tested triazoles was 0.10 mg/L.
  • The method showed high correlation with existing HPLC and referral LC-MS/MS methods, confirmed by Passing Bablok regression and external quality assurance.

Conclusions:

  • The developed LC-MS/MS method offers a rapid and reliable approach for quantifying key antifungal triazoles in plasma.
  • Its efficiency, sensitivity, and accuracy make it ideal for high-throughput clinical laboratories.
  • This method supports optimized therapeutic drug monitoring for patients at risk of invasive fungal infections.
Keywords:
Azole antifungalsItraconazoleLCMSMSPosaconazoleVoriconazole

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