Determination of isavuconazole in rat plasma by UPLC-MS/MS: application to a pharmacokinetic study

Abstract

Isavuconazole (ISA) is a new generation, broad-spectrum triazole with efficacy against invasive fungal diseases including aspergillosis and mucormycosis. In this study, a rapid-resolution UPLC-MS/MS was developed for the determination of isavuconazole in rat plasma. The effective UPLC-MS/MS separation of the examined compounds was applied on a Waters ACQUITY UPLC® BEH C18 column (2.1 mm × 50 mm, 1.7 μm particle size, Waters Corp.) and inline 0.2 mm stainless steel frit filter (Waters Corp.) with a gradient mobile phase system. The assay was validated over a concentration range of 25–2500 ng ml⁻¹ for isavuconazole with a lower limit of quantification (LLOQ) of 25 ng ml⁻¹. The LOD of isavuconazole is 5 ng ml⁻¹ in rat plasma. Stability studies showed that isavuconazole was stable under a variety of storage conditions. This simple and accurate method we developed could be successfully applied to pharmacokinetic studies involving oral administration of isavuconazole to rats and we suggest that it could be applied to human pharmacokinetic studies in the near future.