High-performance liquid chromatographic analysis of the anti-fungal agent SCH 56592 in dog serum

Abstract

SCH 56592 is a novel triazole antifungal agent that is active both orally and intravenously. This compound is in phase II–III clinical trials for the treatment of systemic fungal infections. A high-performance liquid chromatographic (HPLC) method was developed for the analysis of SCH 56592 in serum of dogs, a species used for safety evaluation. The HPLC analysis involved protein precipitation with methanol followed by separation on a C18 column and quantitation by UV absorbance at 262 nm. The method was sensitive with a limit of quantification of 0.05 μg/ml in dog serum. The linearity was satisfactory as indicated by correlations of >0.996, in addition to visual examination of the calibration curves. The precision and accuracy were satisfactory as indicated by coefficients of variation (C.V.) ranging from 2.0 to 3.8%, and bias values ranging from −6.5 to 10%. Moreover, SCH 56592 was stable in dog serum after being subjected to three freeze–thaw cycles. The assay was shown to be sensitive, specific, accurate, precise, and reliable for use in pharmacokinetic or toxicokinetic studies.