title: Determination of Apremilast in Rat Plasma by UPLC-MS-MS and Its Application to a Pharmacokinetic Study.
abstract: 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.
authors.affiliation: Wenzhou People's Hospital, Wenzhou 325000, China.
authors.forename: Lian-Guo
authors.initials: LG
authors.lastname: Chen
authors.affiliation: The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Wenzhou People's Hospital, Wenzhou 325000, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Medical College of Henan University of Science and Technology, Luoyang 471003, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Medical College of Henan University of Science and Technology, Luoyang 471003, China.
authors.forename: Yongyang
authors.initials: Y
authors.lastname: Pan
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China laixixi-001@163.com.
authors.forename: Xixi
authors.initials: X
authors.lastname: Lai
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards; D002851:Chromatography, High Pressure Liquid; D057230:Limit of Detection; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D013792:Thalidomide; C505730:apremilast