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.
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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DOI：
10.1002/bmc.3262
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发表时间：
2015-02
期刊：
影响因子：
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通讯作者：
Yoshiaki Ohtsu;F. Takanuki;Yasuhisa Fukunaga;K. Noguchi
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文献类型：
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作者：
Yoshiaki Ohtsu;F. Takanuki;Yasuhisa Fukunaga;K. Noguchi
强效磷酸二酯酶4抑制剂ASP 3258含有一个羧酸部分和一个萘啶环，是一种新型哮喘和慢性阻塞性肺病治疗药物。为了支持ASP 3258的药物开发，我们开发并验证了一种测定大鼠血浆中ASP 3258的简单方法。加入类似物AS 1406604 -00作为内标物后，在酸性条件下使用C18键合固相萃取柱处理血浆样品，并进样至具有荧光检测的高效液相色谱系统中。采用Shiseido Capcell Pak C18 UG 120色谱柱（3.0 × 150 mm，5 µm），以乙腈-0.5%乙酸（50：50，v/v）为移动的相进行色谱分离。用荧光检测器监测HPLC洗脱液，激发波长设定为315 nm，发射波长设定为365 nm。校准曲线在2.5-250 ng/mL范围内呈线性。验证数据表明，该方法具有选择性、灵敏度和准确度。此外，本方法成功地应用于大鼠血浆样品的药代动力学研究。
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.