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

SCH 56592 is a novel triazole antifungal agent that is active both orally a nd intravenously. This compound is in phase II-m clinical trials for the tr eatment of systemic fungal infections. A high-performance liquid chromatogr aphic (HPLC) method was developed for the analysis of SCH 56592 in serum of dogs, a species used for safety evaluation. The HPLC analysis involved pro tein precipitation with methanol followed by separation on a C-18 column an d quantitation by UV absorbance at 262 nm. The method was sensitive with a limit of quantification of 0.05 mu g/ml in dog serum. The linearity was sat isfactory as indicated by correlations of >0.996, in addition to visual exa mination of the calibration curves. The precision and accuracy were satisfa ctory 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 sta ble in dog serum after being subjected to three freeze-thaw cycles. The ass ay was shown to be sensitive, specific, accurate, precise, and reliable for use in pharmacokinetic or toxicokinetic studies. (C) 2000 Elsevier Science BN. All rights reserved.