학술논문
An automated method for the simultaneous measurement of azole antifungal drugs in human plasma or serum using turbulent flow liquid chromatography-tandem mass spectrometry
Document Type
Academic Journal
Source
Analytical and Bioanalytical Chemistry. August 1, 2012, Vol. 404 Issue 2, p513, 11 p.
Subject
Language
English
ISSN
1618-2642
Abstract
Introduction Development of invasive fungal infections (IFIs) in patients being treated for haematological malignancies is associated with increased morbidity and mortality (1), (2). Due to the difficulty in diagnosing IFIs, [...]
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™ technology offers online, automated sample preparation. An Aria Transcend™ TLX-II coupled with a TSQ Vantage™ MS was used. Centrifuged samples (25 μL) were mixed with internal standard solution (975 μL) and 30 μL injected direct-ly onto a C18-P-XL TurboFlow column. Analytes were fo-cussed 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; vor-iconazole 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.sup.2]>0.99) for all analytes. Inter- and intra-assay imprecision (% RSD) was Keywords TurboFlow MS/MS * Azole antifungals * Itraconazole * Posaconazole * Voriconazole * Automated sample preparation
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™ technology offers online, automated sample preparation. An Aria Transcend™ TLX-II coupled with a TSQ Vantage™ MS was used. Centrifuged samples (25 μL) were mixed with internal standard solution (975 μL) and 30 μL injected direct-ly onto a C18-P-XL TurboFlow column. Analytes were fo-cussed 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; vor-iconazole 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.sup.2]>0.99) for all analytes. Inter- and intra-assay imprecision (% RSD) was Keywords TurboFlow MS/MS * Azole antifungals * Itraconazole * Posaconazole * Voriconazole * Automated sample preparation