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UPLC-MS/MS Technology for the Quantitative Methodology and Pharmacokinetic Analysis of Voxtalisib in Rat Plasma
Voxtalisib, is a specific, effective, and reversible dual inhibitor, which inhibits both pan-class I phosphoinositide 3-kinase (PI3K) and mechanistic target of rapamycin (mTOR). To date, voxtalisib has been studied in trials for melanoma, lymphoma, glioblastoma, breast cancer, and other cancers. In...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237521/ https://www.ncbi.nlm.nih.gov/pubmed/35774599 http://dx.doi.org/10.3389/fphar.2022.914733 |
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author | Li, Qingqing Liu, Ya-nan Wang, Jing Hu, Yingying Hu, Jinyu Xu, Ren-ai Shao, Liu Chen, Lianguo |
author_facet | Li, Qingqing Liu, Ya-nan Wang, Jing Hu, Yingying Hu, Jinyu Xu, Ren-ai Shao, Liu Chen, Lianguo |
author_sort | Li, Qingqing |
collection | PubMed |
description | Voxtalisib, is a specific, effective, and reversible dual inhibitor, which inhibits both pan-class I phosphoinositide 3-kinase (PI3K) and mechanistic target of rapamycin (mTOR). To date, voxtalisib has been studied in trials for melanoma, lymphoma, glioblastoma, breast cancer, and other cancers. In this study, a highly sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technology was applied to the quantitative methodology and pharmacokinetic analysis of voxtalisib in rat plasma. After protein precipitation of the analyte by acetonitrile, the chromatographic separation was performed by gradient elution on an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with acetonitrile (solvent A) and 0.1% formic acid (solvent B) as the mobile phase. In the positive ion mode, the mass transfer detection of the analyte and IS was m/z 270.91 > 242.98 and m/z 572.30 > 246.10, respectively. In the concentration range of 1–2000 ng/ml, a good linear relationship of voxtalisib was successfully established by the UPLC-MS/MS technology, and the lower limit of quantification (LLOQ) of the analyte was identified as 1 ng/ml. Intra-day and inter-day precisions for voxtalisib were 7.5–18.7% and 13.0–16.6%, respectively, and the accuracies were in the ranges of −14.0–2.0% and −7.2–3.1%, respectively. The matrix effect, extraction recovery, carryover and stability of the analyte were all in compliance with the acceptance criteria of bioassays recommended by FDA. Finally, the pharmacokinetic profile of the analyte had been availably studied by the UPLC-MS/MS bio-analytical method after rats were treated by intragastric administration with voxtalisib (5 mg/kg). The results indicated that the UPLC-MS/MS technology can effectively and quickly quantify the analyte, and this method can also be used for the pharmacokinetic study of voxtalisib, which can provide reference for the optimization of clinical drug management in the later period. |
format | Online Article Text |
id | pubmed-9237521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92375212022-06-29 UPLC-MS/MS Technology for the Quantitative Methodology and Pharmacokinetic Analysis of Voxtalisib in Rat Plasma Li, Qingqing Liu, Ya-nan Wang, Jing Hu, Yingying Hu, Jinyu Xu, Ren-ai Shao, Liu Chen, Lianguo Front Pharmacol Pharmacology Voxtalisib, is a specific, effective, and reversible dual inhibitor, which inhibits both pan-class I phosphoinositide 3-kinase (PI3K) and mechanistic target of rapamycin (mTOR). To date, voxtalisib has been studied in trials for melanoma, lymphoma, glioblastoma, breast cancer, and other cancers. In this study, a highly sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technology was applied to the quantitative methodology and pharmacokinetic analysis of voxtalisib in rat plasma. After protein precipitation of the analyte by acetonitrile, the chromatographic separation was performed by gradient elution on an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with acetonitrile (solvent A) and 0.1% formic acid (solvent B) as the mobile phase. In the positive ion mode, the mass transfer detection of the analyte and IS was m/z 270.91 > 242.98 and m/z 572.30 > 246.10, respectively. In the concentration range of 1–2000 ng/ml, a good linear relationship of voxtalisib was successfully established by the UPLC-MS/MS technology, and the lower limit of quantification (LLOQ) of the analyte was identified as 1 ng/ml. Intra-day and inter-day precisions for voxtalisib were 7.5–18.7% and 13.0–16.6%, respectively, and the accuracies were in the ranges of −14.0–2.0% and −7.2–3.1%, respectively. The matrix effect, extraction recovery, carryover and stability of the analyte were all in compliance with the acceptance criteria of bioassays recommended by FDA. Finally, the pharmacokinetic profile of the analyte had been availably studied by the UPLC-MS/MS bio-analytical method after rats were treated by intragastric administration with voxtalisib (5 mg/kg). The results indicated that the UPLC-MS/MS technology can effectively and quickly quantify the analyte, and this method can also be used for the pharmacokinetic study of voxtalisib, which can provide reference for the optimization of clinical drug management in the later period. Frontiers Media S.A. 2022-06-14 /pmc/articles/PMC9237521/ /pubmed/35774599 http://dx.doi.org/10.3389/fphar.2022.914733 Text en Copyright © 2022 Li, Liu, Wang, Hu, Hu, Xu, Shao and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Li, Qingqing Liu, Ya-nan Wang, Jing Hu, Yingying Hu, Jinyu Xu, Ren-ai Shao, Liu Chen, Lianguo UPLC-MS/MS Technology for the Quantitative Methodology and Pharmacokinetic Analysis of Voxtalisib in Rat Plasma |
title | UPLC-MS/MS Technology for the Quantitative Methodology and Pharmacokinetic Analysis of Voxtalisib in Rat Plasma |
title_full | UPLC-MS/MS Technology for the Quantitative Methodology and Pharmacokinetic Analysis of Voxtalisib in Rat Plasma |
title_fullStr | UPLC-MS/MS Technology for the Quantitative Methodology and Pharmacokinetic Analysis of Voxtalisib in Rat Plasma |
title_full_unstemmed | UPLC-MS/MS Technology for the Quantitative Methodology and Pharmacokinetic Analysis of Voxtalisib in Rat Plasma |
title_short | UPLC-MS/MS Technology for the Quantitative Methodology and Pharmacokinetic Analysis of Voxtalisib in Rat Plasma |
title_sort | uplc-ms/ms technology for the quantitative methodology and pharmacokinetic analysis of voxtalisib in rat plasma |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237521/ https://www.ncbi.nlm.nih.gov/pubmed/35774599 http://dx.doi.org/10.3389/fphar.2022.914733 |
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