title: 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 microg/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.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: P
authors.initials: P
authors.lastname: Likhari
authors.forename: P
authors.initials: P
authors.lastname: Kumari
authors.forename: C C
authors.initials: CC
authors.lastname: Lin
authors.forename: A A
authors.initials: AA
authors.lastname: Nomeir
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000097:blood*; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D004355:Drug Stability; D005615:Freezing; D016014:Linear Models; D000432:Methanol; D008832:Microchemistry; D011786:Quality Control; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D014230:Triazoles / Q000097:blood*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D000432:Methanol