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Determination and pharmacokinetic study of thyroid hormone receptor-β agonist resmetirom in beagle dogs using
Songmao Liang1, Mingxuan Li1, Xu Gong1
1Innovation Practice Platform for College Student, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471023, PR China.
Abstract:
A HPLC-MS/MS method for determination of thyroid hormone receptor-β agonist resmetirom was established and validated, and pharmacokinetic study was conducted in beagle dogs after oral administration. Methanol-0.1 % formic acid was used as the mobile phase, resmetirom and carbamazepine (internal standard, IS) were separated on a VP-ODS C18 column. During the MS detection process, multiple reaction monitoring (MRM) in electrospray positive ion mode was used. The quantitative ions were m/z 435.10→182.05 for resmetirom, and m/z 237.30→194.30 for IS. The linear range of resmetirom was 1-200 ng/mL, with correlation coefficients greater than 0.999 8. The precision RSD values of resmetirom were 3.14-8.42 % and 2.74-7.87 %, respectively. The accuracy values were around 100 %. The recovery of resmetirom were greater than 80.39 %. At the same time, resmetirom were stable under the experimental conditions. After oral administration of resmetirom to the beagle dogs, the Cmax of resmetirom was about 802.40 ng/mL at about 3.33 h, the t1/2 of resmetirom was about 4.58 h.
