Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, in Rats by UPLC-MS/MS
Version 2 2024-06-19, 21:13Version 2 2024-06-19, 21:13
Version 1 2023-10-10, 05:28Version 1 2023-10-10, 05:28
journal contribution
posted on 2024-06-19, 21:13authored byBo Wang, Feifei ChenFeifei Chen, Quan Zhou, Yunfang Zhou, Deru Meng, Peiwu Geng, Ailian Hua, Weiping Ji, Changxiong Wang, Shuanghu Wang, Liming Hu
Lusutrombopag is a second oral thrombopoietin (TPO) receptor agonist that selectively acts on human TPO receptors. In the study, UPLC-MS/MS was used to establish a selective and sensitive method to determine lusutrombopag with poziotinib as IS (internal standard) in rat plasma. Samples were prepared by precipitating protein with acetonitrile as a precipitant. Separation of lusutrombopag and poziotinib was performed on a CORTECS UPLC C18 column (2.1 ∗ 50 mm, 1.6 μm). The mobile phase (acetonitrile and water containing 0.1% formic acid) with gradient elution was set at a flow rate of 0.4 ml/min. The mass spectrometric measurement was conducted under positive ion mode using multiple reaction monitoring (MRM) of m/z 592.97 ⟶ 491.02 for lusutrombopag and m/z for poziotinib (IS) 492.06 ⟶ 354.55. The linear calibration curve of the concentration range was 2–2000 ng/ml for lusutrombopag, with a lower limit of quantification (LLOQ) of 2 ng/ml. RSD of interday and intraday precision were both no more than 9.66% with the accuracy ranging from 105.82% to 108.27%. The extraction recovery of lusutrombopag was between 82.15% and 90.34%. The developed and validated method was perfectly used in the pharmacokinetic study of lusutrombopag after oral administration in rats.