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

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 onlin...

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Bibliographic Details
Published in:Analytical and bioanalytical chemistry 2012-08, Vol.404 (2), p.513-523
Main Authors: Couchman, L., Buckner, S. L., Morgan, P. E., Ceesay, M. M., Pagliuca, A., Flanagan, R. J.
Format: Article
Language:English
Subjects:
Analysis
Analytical Chemistry
Antifungal Agents - blood
Aspergillus
Automated
Automation
Azoles
Azoles - blood
Biochemistry
Calibration
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Chromatography, Liquid - methods
Drugs
Fluconazole
Food Science
Health aspects
Humans
Itraconazole
Laboratory Medicine
Liquid chromatography
Mathematical analysis
Measurement
Methods
Methyl alcohol
Monitoring
Monitoring/Environmental Analysis
Mycoses
Original Paper
Phenyls
Reference Standards
Tandem Mass Spectrometry - methods
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Summary: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 μL) were mixed with internal standard solution (975 μL) and 30 μL 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
ISSN:1618-2642
1618-2650
DOI:10.1007/s00216-012-6176-3