An automated method for the simultaneous measurement of azole antifungal drugs in human plasma or serum using turbulent flow liquid chromatography-tandem mass spectrometry

L. Couchman*, S. L. Buckner, P. E. Morgan, M. M. Ceesay, A. Pagliuca, R. J. Flanagan

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    29 Citations (Scopus)

    Abstract

    Azole antifungal drugs are important in the prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring may be indicated to (1) monitor adherence, (2) guide dosage and (3) minimise the risk of drug-drug interactions and dose-related toxicity. TurboFlow(TM) technology offers online, automated sample preparation. An Aria Transcend(TM) TLX-II coupled with a TSQ Vantage(TM) MS was used. Centrifuged samples (25 mu L) were mixed with internal standard solution (975 mu L) and 30 mu L injected directly onto a C18-P-XL TurboFlow column. Analytes were focussed onto a Phenomenex Gemini Phenyl analytical column and eluted using a methanol/water gradient (flow-rate, 0.8 mL/min). Analytes were monitored in selected reaction monitoring mode (two transitions per analyte, positive mode APCI). Calibration ranges were as follows: itraconazole, hydroxyitraconazole, and posaconazole 0.05-5.0 mg/L; voriconazole and fluconazole 0.1-10 mg/L. Total analysis time was 12 min. TurboFlow column recovery was > 77% for all analytes. Calibration was linear (R (2) > 0.99) for all analytes. Inter- and intra-assay imprecision (% RSD) was <8% and accuracy (nominal internal quality control values) 90-105% for all analytes. The limit of detection was 0.01 mg/L for all analytes. No matrix effects were observed. This method is simple, robust and suitable for measuring these compounds at concentrations attained during therapy.

    Original languageEnglish
    Pages (from-to)513-523
    Number of pages11
    JournalANALYTICAL AND BIOANALYTICAL CHEMISTRY
    Volume404
    Issue number2
    DOIs
    Publication statusPublished - Aug 2012

    Keywords

    • TurboFlow MS/MS
    • Azole antifungals
    • Itraconazole
    • Posaconazole
    • Voriconazole
    • Automated sample preparation
    • INVASIVE FUNGAL-INFECTIONS
    • CELL TRANSPLANT RECIPIENTS
    • ORAL POSACONAZOLE
    • ITRACONAZOLE
    • PHARMACOKINETICS
    • VORICONAZOLE
    • PROPHYLAXIS
    • SAFETY
    • HYDROXYITRACONAZOLE
    • MALIGNANCIES

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