Determination and pharmacokinetic study of thyroid hormone receptor-β agonist resmetirom in beagle dogs using HPLC-MS/MS method

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 C_max of resmetirom was about 802.40 ng/mL at about 3.33 h, the t_1/2 of resmetirom was about 4.58 h.