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Simultaneous Determination of Orelabrutinib, Zanubrutinib, Ibrutinib and Its Active Metabolite in Human Plasma Using LC-MS/MS

Ibrutinib, orelabrutinib, and zanubrutinib are all Bruton’s tyrosine kinase inhibitors, which have greatly improved the treatment of B-cell malignancies. In this study, an LC-MS/MS method was developed and validated for the determination of orelabrutinib, zanubrutinib, ibrutinib, and its active meta...

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Autores principales: Sun, Lu-Ning, Zhao, Yang, Qian, Zhou-Yi, Chen, Xiang-Long, Ma, Hong, Guo, Yu-Jiao, Shen, Hao, Wang, Yong-Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9920560/
https://www.ncbi.nlm.nih.gov/pubmed/36770870
http://dx.doi.org/10.3390/molecules28031205
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author Sun, Lu-Ning
Zhao, Yang
Qian, Zhou-Yi
Chen, Xiang-Long
Ma, Hong
Guo, Yu-Jiao
Shen, Hao
Wang, Yong-Qing
author_facet Sun, Lu-Ning
Zhao, Yang
Qian, Zhou-Yi
Chen, Xiang-Long
Ma, Hong
Guo, Yu-Jiao
Shen, Hao
Wang, Yong-Qing
author_sort Sun, Lu-Ning
collection PubMed
description Ibrutinib, orelabrutinib, and zanubrutinib are all Bruton’s tyrosine kinase inhibitors, which have greatly improved the treatment of B-cell malignancies. In this study, an LC-MS/MS method was developed and validated for the determination of orelabrutinib, zanubrutinib, ibrutinib, and its active metabolite dihydrodiol ibrutinib in human plasma. The Ibrutinib-d5 was used as the internal standard. Pretreatment was performed using a simple protein precipitation step using acetonitrile. The ACQUITY UPLC HSS T3 column (2.1×50 mm, 1.8 μm) was used to separate the analytes, and the run time was 6.5 min. The mobile phase consisted of acetonitrile and 10 mM of ammonium formate, which contained 0.1% formic acid. The multiple reactions’ monitoring transitions were selected at m/z 428.1→411.2, 472.2→455.2, 441.1→304.2, 475.2→304.2 and 446.2→309.2 respectively for orelabrutinib, zanubrutinib, ibrutinib, dihydrodiol ibrutinib and ibrutinib-d5 using positive ion electrospray ionization. The standard curves were linear, from 0.400 to 200 ng/mL for ibrutinib and dihydrodiol ibrutinib, 1.00–500 ng/mL for orelabrutinib, and 2.00–1000 ng/mL for zanubrutinib. Selectivity, the lower limit of quantitation, precision, accuracy, matrix effect, recovery, stability, and dilution integrity all met the acceptance criteria of FDA guidance. This method was used to quantify the plasma levels of orelabrutinib, zanubrutinib, ibrutinib, and dihydrodiol ibrutinib in clinical patients.
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spelling pubmed-99205602023-02-12 Simultaneous Determination of Orelabrutinib, Zanubrutinib, Ibrutinib and Its Active Metabolite in Human Plasma Using LC-MS/MS Sun, Lu-Ning Zhao, Yang Qian, Zhou-Yi Chen, Xiang-Long Ma, Hong Guo, Yu-Jiao Shen, Hao Wang, Yong-Qing Molecules Article Ibrutinib, orelabrutinib, and zanubrutinib are all Bruton’s tyrosine kinase inhibitors, which have greatly improved the treatment of B-cell malignancies. In this study, an LC-MS/MS method was developed and validated for the determination of orelabrutinib, zanubrutinib, ibrutinib, and its active metabolite dihydrodiol ibrutinib in human plasma. The Ibrutinib-d5 was used as the internal standard. Pretreatment was performed using a simple protein precipitation step using acetonitrile. The ACQUITY UPLC HSS T3 column (2.1×50 mm, 1.8 μm) was used to separate the analytes, and the run time was 6.5 min. The mobile phase consisted of acetonitrile and 10 mM of ammonium formate, which contained 0.1% formic acid. The multiple reactions’ monitoring transitions were selected at m/z 428.1→411.2, 472.2→455.2, 441.1→304.2, 475.2→304.2 and 446.2→309.2 respectively for orelabrutinib, zanubrutinib, ibrutinib, dihydrodiol ibrutinib and ibrutinib-d5 using positive ion electrospray ionization. The standard curves were linear, from 0.400 to 200 ng/mL for ibrutinib and dihydrodiol ibrutinib, 1.00–500 ng/mL for orelabrutinib, and 2.00–1000 ng/mL for zanubrutinib. Selectivity, the lower limit of quantitation, precision, accuracy, matrix effect, recovery, stability, and dilution integrity all met the acceptance criteria of FDA guidance. This method was used to quantify the plasma levels of orelabrutinib, zanubrutinib, ibrutinib, and dihydrodiol ibrutinib in clinical patients. MDPI 2023-01-26 /pmc/articles/PMC9920560/ /pubmed/36770870 http://dx.doi.org/10.3390/molecules28031205 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sun, Lu-Ning
Zhao, Yang
Qian, Zhou-Yi
Chen, Xiang-Long
Ma, Hong
Guo, Yu-Jiao
Shen, Hao
Wang, Yong-Qing
Simultaneous Determination of Orelabrutinib, Zanubrutinib, Ibrutinib and Its Active Metabolite in Human Plasma Using LC-MS/MS
title Simultaneous Determination of Orelabrutinib, Zanubrutinib, Ibrutinib and Its Active Metabolite in Human Plasma Using LC-MS/MS
title_full Simultaneous Determination of Orelabrutinib, Zanubrutinib, Ibrutinib and Its Active Metabolite in Human Plasma Using LC-MS/MS
title_fullStr Simultaneous Determination of Orelabrutinib, Zanubrutinib, Ibrutinib and Its Active Metabolite in Human Plasma Using LC-MS/MS
title_full_unstemmed Simultaneous Determination of Orelabrutinib, Zanubrutinib, Ibrutinib and Its Active Metabolite in Human Plasma Using LC-MS/MS
title_short Simultaneous Determination of Orelabrutinib, Zanubrutinib, Ibrutinib and Its Active Metabolite in Human Plasma Using LC-MS/MS
title_sort simultaneous determination of orelabrutinib, zanubrutinib, ibrutinib and its active metabolite in human plasma using lc-ms/ms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9920560/
https://www.ncbi.nlm.nih.gov/pubmed/36770870
http://dx.doi.org/10.3390/molecules28031205
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