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

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...

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Main Authors: Bo Wang, Feifei Chen, Quan Zhou, Yunfang Zhou, Deru Meng, Peiwu Geng, Ailian Hua, Weiping Ji, Changxiong Wang, Shuanghu Wang, Liming Hu
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:International Journal of Analytical Chemistry
Online Access:http://dx.doi.org/10.1155/2020/7290470
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author Bo Wang
Feifei Chen
Quan Zhou
Yunfang Zhou
Deru Meng
Peiwu Geng
Ailian Hua
Weiping Ji
Changxiong Wang
Shuanghu Wang
Liming Hu
author_facet Bo Wang
Feifei Chen
Quan Zhou
Yunfang Zhou
Deru Meng
Peiwu Geng
Ailian Hua
Weiping Ji
Changxiong Wang
Shuanghu Wang
Liming Hu
author_sort Bo Wang
collection DOAJ
description 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.
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language English
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publisher Wiley
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spelling doaj-art-75de963c83524cb1857a5b4a53ccc0362025-08-20T02:06:58ZengWileyInternational Journal of Analytical Chemistry1687-87601687-87792020-01-01202010.1155/2020/72904707290470Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, in Rats by UPLC-MS/MSBo Wang0Feifei Chen1Quan Zhou2Yunfang Zhou3Deru Meng4Peiwu Geng5Ailian Hua6Weiping Ji7Changxiong Wang8Shuanghu Wang9Liming Hu10Department of Orthopaedics, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui 323000, Zhejiang, ChinaThe Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui 323000, Zhejiang, ChinaThe Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui 323000, Zhejiang, ChinaThe Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui 323000, Zhejiang, ChinaThe Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui 323000, Zhejiang, ChinaThe Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui 323000, Zhejiang, ChinaThe Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui 323000, Zhejiang, ChinaDepartment of Orthopaedics, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui 323000, Zhejiang, ChinaThe Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui 323000, Zhejiang, ChinaThe Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui 323000, Zhejiang, ChinaDepartment of Pharmacy, The First People’s Hospital of Wenling, Wenling 317500, Zhejiang, ChinaLusutrombopag 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.http://dx.doi.org/10.1155/2020/7290470
spellingShingle Bo Wang
Feifei Chen
Quan Zhou
Yunfang Zhou
Deru Meng
Peiwu Geng
Ailian Hua
Weiping Ji
Changxiong Wang
Shuanghu Wang
Liming Hu
Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, in Rats by UPLC-MS/MS
International Journal of Analytical Chemistry
title Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, in Rats by UPLC-MS/MS
title_full Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, in Rats by UPLC-MS/MS
title_fullStr Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, in Rats by UPLC-MS/MS
title_full_unstemmed Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, in Rats by UPLC-MS/MS
title_short Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, in Rats by UPLC-MS/MS
title_sort pharmacokinetics of lusutrombopag a novel thrombopoietin receptor agonist in rats by uplc ms ms
url http://dx.doi.org/10.1155/2020/7290470
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