Article (Scientific journals)
Simultaneous determination of seven azole antifungal drugs in serum by ultra-high pressure liquid chromatography and diode array detection
MISTRETTA, Virginie; DUBOIS, Nathalie; DENOOZ, Raphael et al.
2014In Acta Clinica Belgica, 69 (1), p. 53-61
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Keywords :
azole antifungal drugs; therapeutic drug monitoring,; UHPLC-DAD; human serum; clinical practice
Abstract :
[en] Azole antifungals are a group of fungistatic agents that can be administered orally or parenterally. The determination of the concentrations of these antifungals (miconazole, fluconazole, ketoconazole, posaconazole, voriconazole, itraconazole, and its major active metabolite, hydroxy-itraconazole) in serum can be useful to adapt the doses to pharmacological ranges because of large variability in the absorption and metabolism of the drugs, multiple drug interactions, but also potential resistance or toxicity. A method was developed and validated for the simultaneous determination of these drugs in serum utilizing ultra-high pressure liquid chromatography and diode array detection (UHPLC-DAD). After a simple and rapid liquid– liquid extraction, the pre-treated sample was analysed on an UHPLC-DAD system (Waters CorporationH). The chromatographic separation was carried out on an Acquity BEH C18 column (Waters Corporation) with a gradient mode of mobile phase composed of acetonitrile and aqueous ammonium bicarbonate 10.0 M pH10. The flow rate was 0.4 ml/min and the injection volume was 5 ml. The identification wavelength varied according to the drug from 210 to 260 nm. The method was validated by the total error method approach by using an analytical validation software (eNnoval V3.0 ArlendaH). The seven azole antifungals were identified by retention time and specific UV spectra, over a 13-minute run time. All calibration curves showed good linearity (r2.0.99) in ranges considered clinically adequate. The assay was linear from 0.05 to 10 mg/l for voriconazole, posaconazole, itraconazole, hydroxy-itraconazole, and ketoconazole, from 0.3 to 10 mg/l for fluconazole, and from 0.1 to 10 mg/l for miconazole. The bias and imprecision values for intraand inter-assays were lower than 10% and than 15%, respectively. In conclusion, a simple, sensitive, and selective UHPLC-DAD method was developed and validated to determine seven azole antifungal drugs in human serum. This method is applicable to patient samples, and can be applied successfully to clinical applications and therapeutic drug monitoring.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
MISTRETTA, Virginie ;  Centre Hospitalier Universitaire de Liège - CHU > Toxicologie clinique
DUBOIS, Nathalie ;  Centre Hospitalier Universitaire de Liège - CHU > Toxicologie clinique
DENOOZ, Raphael ;  Centre Hospitalier Universitaire de Liège - CHU > Toxicologie clinique
Charlier, Corinne  ;  Université de Liège - ULiège > Département de pharmacie > Chimie toxicologique
Language :
English
Title :
Simultaneous determination of seven azole antifungal drugs in serum by ultra-high pressure liquid chromatography and diode array detection
Publication date :
March 2014
Journal title :
Acta Clinica Belgica
ISSN :
0001-5512
Publisher :
Acta Clinica Belgica, Bruxelles, Belgium
Volume :
69
Issue :
1
Pages :
53-61
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 20 January 2014

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