title: Determination of ASP3258, a novel phosphodiesterase type 4 inhibitor, in rat plasma by high-performance liquid chromatography with fluorescence detection and its application to pharmacokinetic study.
abstract: The potent phosphodiesterase 4 inhibitor ASP3258 contains a carboxylic acid moiety and a naphthyridine ring and is a novel therapeutic agent for asthma and chronic obstructive pulmonary disease. To support the drug development of ASP3258, we developed and validated a simple method for its determination in rat plasma. Following the addition of the analog AS1406604-00 as an internal standard, plasma samples were processed using C18 -bonded solid-phase extraction cartridges under acidic conditions and injected into a high-performance liquid chromatography system with fluorescence detection. Chromatographic separation was achieved on a Shiseido Capcell Pak C18 UG120 column (3.0 × 150 mm, 5 µm) with a mobile phase consisting of acetonitrile-0.5% acetic acid (50:50, v/v). HPLC eluent was monitored with a fluorescence detector set at a wavelength of 315 nm for excitation and 365 nm for emission. The calibration curve was linear over a range of 2.5-250 ng/mL. Validation data demonstrated that the method is selective, sensitive and accurate. In addition, the present method was successfully applied to rat plasma samples from a pharmacokinetic study.
authors.affiliation: Drug Metabolism Research Laboratories, Astellas Pharma Inc., Osaka, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohtsu
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Takanuki
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fukunaga
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008297:Male; D009287:Naphthyridines / Q000097:blood / Q000493:pharmacokinetics*; D058988:Phosphodiesterase 4 Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D052616:Solid Phase Extraction
chemical_list: C561429:3-(4-(3-chlorophenyl)-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl)propanoic acid; D009287:Naphthyridines; D058988:Phosphodiesterase 4 Inhibitors
keywords: ASP3258; HPLC; fluorescence detection; pharmacokinetics; rat plasma