Measurement of posaconazole, itraconazole, and hydroxyitraconazole in plasma/serum by high-performance liquid chromatography with fluorescence detection.
Ther Drug Monit
; 33(6): 735-41, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-22105591
ABSTRACT
BACKGROUND:
Itraconazole and posaconazole are used in the prevention and treatment of invasive fungal infections. However, the oral bioavailability of both compounds varies widely, and dose-serum concentration relationships are poorly defined for these analytes. The aim of this work was to develop and validate a simple assay that could be implemented in most laboratories for the purpose of therapeutic drug monitoring.METHODS:
Calibrators (n = 7) and internal quality control solutions (n = 3) were prepared in pooled human serum. Sample (100 µL), internal standard solution (25 µL), Tris solution (2 mol/L; pH 10.6), and extraction solvent (methyl tert-butyl ether, 600 µL) were vortex mixed and centrifuged. The solvent layer was removed and evaporated to dryness and the residue reconstituted in watermethanol (1 + 3, 50 µL). A portion (5 µL) of the reconstituted extract was analyzed using a 3-µm Gemini C6 phenyl column with fluorescence detection (excitation 260 nm, emission 350 nm). The method was used to measure itraconazole and hydroxyitraconazole, or posaconazole, in serum samples taken 1-2 hours before the next dose, from patients forming part of a study into management and diagnostic strategies for invasive aspergillosis.RESULTS:
Response was linear over the calibration ranges. Accuracy and imprecision were 92-111.4% and 3.2-13.4% (relative standard deviation), respectively. No interferences were noted. There was a good agreement with nominal values of each analyte in an external quality assessment scheme. In patients prescribed either 400 mg/d of itraconazole (n = 46) or 600-800 mg/d of posaconazole (n = 28) only 24% and 7% of samples, respectively, had serum itraconazole or posaconazole concentrations above the target threshold suggested in published guidelines.CONCLUSIONS:
A simple, sensitive high-performance liquid chromatographic method has been developed for the analysis of itraconazole, hydroxyitraconazole, and posaconazole in serum/plasma. Few of the samples measured from patients participating in the clinical study attained concentrations of the drug/metabolite in serum that have been recommended for effective antifungal therapy.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Triazóis
/
Itraconazol
/
Antifúngicos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article