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  after administration of single doses.

中文翻译：

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UPLC-MS-MS定量测定比格犬血浆中菊粉的含量及其在药代动力学研究中的应用

建立了灵敏且选择性的超高效液相色谱-串联质谱法（UPLC-MS-MS）测定比格犬血浆中的阿米司特，并在当前研究中成功进行了验证。氯吡格雷用作内标（IS），叔丁基甲基醚液-液萃取用于样品制备。在UPLC BEH Shield RP18色谱柱上进行色谱分离（50 mm×2.1 mm，  1.7μm）用5 mM甲酸铵水和5 mM甲酸铵甲醇作为流动相进行梯度洗脱。比格犬血浆中的apremilast的校准图在2-3000 ng / mL范围内是线性的。在比格犬血浆中平均阿普利司特的回收率为87.4％至97.4％。批内和批间精度分别小于6％和9％，精度在92.4％和101.1％之间。该方法也已经成功地用于阿普司特的药代动力学研究。口服后，比格犬30 mg·day ^-1的平均t1 / 2Z为5.41 h 。单剂量给药后，AUC0-t从3.51线性增加至1802.13  。