Abstract

Voriconazole, an antifungal drug exhibiting wide inter-individual variability, is an ideal candidate for therapeutic drug monitoring (TDM). The aim of the present study was to standardize a simple, sensitive and rapid high performance liquid chromatography (HPLC) method with ultraviolet detection to determine plasma voriconazole concentration. The HPLC method consisted of a combination of acetonitrile and water (7:3) as mobile phase with 1ml/min flow rate and detection at 255nm. Plasma protein precipitation was carried out using perchloric acid and the filtered supernatant was passed through C18 column (250×4.6mm, 5μm) for the separation of voriconazole. The limit of quantification of voriconazole was 0.2mg/L. The assay was validated with a linearity of 0.2-15mg/L and used clinically for TDM in patient samples. The inter-assay precision was below 15% for routine quality control samples. Weight based voriconazole doses were prescribed to 26 patients for empirical treatment of invasive fungal infections. Voriconazole therapy was managed from the baseline drug levels and follow up analysis reflected achievement in clinical efficacy. Routine TDM of voriconazole may reduce adverse events and improve the treatment response in invasive fungal infections.

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