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Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, in Rats by UPLC-MS/MS

Version 2 2024-06-19, 21:13
Version 1 2023-10-10, 05:28
journal contribution
posted on 2024-06-19, 21:13 authored by Bo 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.

History

Journal

International Journal of Analytical Chemistry

Volume

2020

Article number

7290470

Pagination

1-6

Location

London, Eng.

ISSN

1687-8779

eISSN

1687-8779

Language

English

Publication classification

C1.1 Refereed article in a scholarly journal

Publisher

Hindawi

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