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

Authors :
Lu-Ning Sun
Yang Zhao
Zhou-Yi Qian
Xiang-Long Chen
Hong Ma
Yu-Jiao Guo
Hao Shen
Yong-Qing Wang
Source :
Molecules, Vol 28, Iss 3, p 1205 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

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.

Details

Language :
English
ISSN :
14203049
Volume :
28
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.6e0ab926602645f7bfa06aaca45bf541
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules28031205