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摘要
Apremilast is a novel, orally administered inhibitor of the intracellular enzyme, phosphodiesterase 4 (PDE4). In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method-for determination of apremilast in rat plasma was-developed and validated. After addition of diazepam as an internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 x 100 mm, 1.7 mu m) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 483.1 -> 478.1 for apremilast, and m/z 285.1 -> 493.1 for IS. Calibration plots were linear throughout the range 2-2000 ng/mL for apremilast in rat plasma. Mean recoveries of apremilast hi rat plasma ranged from 87.8% to 90.4%. RSD of intra-day and inter-day precision were both < 6%. The accuracy of the method was between 96.0% and 107.5%. The method was successfully applied to pharmacokinetic study of apremilast after either oral or intravenous administration. The bioavailability of apremilast was reported as 14.5%.
- 出版日期2015-9
- 单位温州医科大学
