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Development and Validation of a Liquid Chromatography - Tandem Mass Spectrometry Method for the Determination of Voriconazole and Posaconazole in Serum Samples from Patients with Invasive Mycoses

Abstract

Loretta Franceschi, Sara D’Aronco and Mario Furlanut

Posaconazole and voriconazole, two triazole antifungal agents, are used for the prophylaxis and treatment of invasive mycoses in patients with acute myeloid leukaemia and/or immunocompromised. Inter- and intra-patient variability of pharmacokinetics, drug-drug interactions, serum concentration related toxicity and success of therapy has stressed the need of frequently therapeutic drug monitoring of both drugs. Therefore, a rapid, selective and sensitive isocratic reversed-phase HPLC assay coupled with Mass spectrometry detection for quantification of posaconazole and voriconazole in serum samples has been developed.

Analytes were extracted on solid-phase cartridges (SPE) and chromatographic separation was achieved on a C8 column and detected by mass spectrometry in positive ion mode with the select ion monitoring (SIM) mode. The total chromatographic running time was 6 minutes. The method was successfully used for a pharmacokinetic study but, thanks to its rapidity and selectivity, it’s also suitable for routinarly therapeutic drug monitoring (TDM).

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