Abstract
A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of apremilast in beagle dog plasma has been developed and successfully validated in the current study. Clopidogrel was employed as an internal standard (IS), and liquid-liquid extraction by tert-butylmethyl ether was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH Shield RP18 column (50 mm × 2.1 mm, 1.7 μm) with 5 mM ammonium formate water and 5 mM ammonium formate methanol as the mobile phase with gradient elution. Calibration plots were linear in the range of 2–3000 ng/mL for apremilast in beagle dog plasma. Mean recoveries of apremilast in beagle dogs plasma ranged from 87.4% to 97.4%. The intrarun and interrun precision was less than 6% and 9%, respectively, with the accuracy between 92.4% and 101.1%. The method has also been successfully applied in the pharmacokinetics study of apremilast. The mean t1/2Z was 5.41 h for 30 mg·day−1 for beagle dogs after oral administration. The AUC0-t increased linearly from 3.51 to 1802.13 μg L−1∗h after administration of single doses.
Highlights
Psoriasis and/or psoriatic arthritis (PsA), prevalent in an estimated 2-3% of worldwide population [1, 2], is a kind of the chronic inflammatory disease process driven by overproduction of inflammatory mediators released by innate and adaptive immune cells [3, 4]
Interday precision, and accuracy were determined by analyzing QC samples at three concentrations (5, 50, and 1000 ng·mL−1, n 6) on three separated days. e precision was defined as the relative standard deviation (RSD) of QC sample concentrations determined at 6 replicates, whereas accuracy was assessed as the percentage to the nominal concentration (%)
The Rt of apremilast on the BEH Shield RP18 column (1.49 min) was more appropriate than that of the BEH C18 (
Summary
Psoriasis and/or psoriatic arthritis (PsA), prevalent in an estimated 2-3% of worldwide population [1, 2], is a kind of the chronic inflammatory disease process driven by overproduction of inflammatory mediators released by innate and adaptive immune cells [3, 4]. Phosphodiesterase 4 (PDE4) is a principle enzyme dominant in immune cells and modulates the production of these cytokinins such as interleukin- (IL-) 17, IL-23, and tumour necrosis factor (TNF), as well as anti-inflammatory mediators such as IL-10. Apremilast is an oral PDE4 inhibitor recently approved by FDA as the first-line treatment of PsA in the USA and by the Drug Controller General of India for marketing in India [5]. As a substrate of CYP3A4 enzyme, apremilast may interact with CYP3A4 enzyme inducers, and a reliable validated assay is necessary for the therapeutic monitoring and to avoid any possible pharmacokinetic (PK) interactions
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