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 |
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| Authors: | Yoshiaki Ohtsu Fumiyo Takanuki Yasuhisa Fukunaga Kiyoshi Noguchi |
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| Affiliation: | 1. Drug Metabolism Research Laboratories, Astellas Pharma Inc., Osaka, Japan;2. Analysis and Pharmacokinetics Research Division, Astellas Research Technologies Co. Ltd, Tsukuba, Japan;3. Analysis and Pharmacokinetics Research Laboratories, Astellas Pharma Inc., Tsukuba, Japan |
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| 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. Copyright © 2014 John Wiley & Sons, Ltd. |
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| Keywords: | ASP3258 pharmacokinetics rat plasma HPLC fluorescence detection |
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