Determination of Apremilast in Rat Plasma by UPLC–MS-MS and Its Application to a Pharmacokinetic Study

• Published in: Journal of chromatographic science Vol. 54; no. 8; pp. 1336 - 1340
• Main Authors: Chen, Lian-guo, Wang, Zhe, Wang, Shujun, Li, Tao, Pan, Yongyang, Lai, Xixi
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.09.2016
• Subjects: Animals; Blood Chemical Analysis - methods; Blood Chemical Analysis - standards; Chromatography, High Pressure Liquid; Limit of Detection; Pharmacokinetics; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Tandem Mass Spectrometry; Thalidomide - analogs & derivatives; Thalidomide - blood; Thalidomide - pharmacokinetics
• ISSN: 0021-9665; 1945-239X
• DOI: 10.1093/chromsci/bmw072

A rapid, sensitive and selective ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS-MS) was developed and validated for the determination and pharmacokinetic investigation of apremilast in rat plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2 mL of acetonitrile to a 0.1 mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile–0.1% formic acid in water with gradient elution. The total run time was 3.0 min, and the elution of apremilast was at 1.27 min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring mode using the respective transitions m/z 461.3 → 257.1 for apremilast and m/z 237.2 → 194.2 for carbamazepine (internal standard). The calibration curve was linear over the range of 0.1–100 ng/mL with a lower limit of quantitation of 0.1 ng/mL. The mean recovery of apremilast in plasma was in the range of 83.2–87.5%. Both intraday and interday precision were <9.6%. This method was successfully applied in the pharmacokinetic study after oral administration of 6.0 mg/kg apremilast in rats.