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Simple, sensitive and rapid determination of linifanib (ABT-869), a novel tyrosine kinase inhibitor in rat plasma by UHPLC-MS/MS
BACKGROUND: Linifanib (ABT-869) is an orally active receptor tyrosine kinase inhibitor, which simultaneously inhibits vascular endothelial and platelet derived growth factor receptor. The aim of the present study was to develop an UHPLC-MS/MS method for the quantification of linifanib in rat plasma...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932137/ https://www.ncbi.nlm.nih.gov/pubmed/24533632 http://dx.doi.org/10.1186/1752-153X-8-13 |
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author | Iqbal, Muzaffar Ezzeldin, Essam Wani, Tanveer A Khalil, Nasr Y |
author_facet | Iqbal, Muzaffar Ezzeldin, Essam Wani, Tanveer A Khalil, Nasr Y |
author_sort | Iqbal, Muzaffar |
collection | PubMed |
description | BACKGROUND: Linifanib (ABT-869) is an orally active receptor tyrosine kinase inhibitor, which simultaneously inhibits vascular endothelial and platelet derived growth factor receptor. The aim of the present study was to develop an UHPLC-MS/MS method for the quantification of linifanib in rat plasma to support the pharmacokinetic and toxicokinetic studies. RESULTS: Linifanib was separated on Acquity UPLC BEH™ C(18) column (50 × 2.1 mm, i.d. 1.7 μm) using acetonitrile-10 mM ammonium acetate (60:40, v/v) as an isocratic mobile phase at a flow rate of 0.3 mL/min with sunitinib as internal standard (IS). Detection was performed on tandem mass spectrometer using electrospray ionization source in positive mode by multiple reaction monitoring. The monitored transitions were set at m/z 376.05 > 250.97 for linifanib and m/z 399.12 >283.02 for IS, respectively. Both linifanib and IS were eluted at 0.68 and 0.44 min, respectively with a total run time of 2.0 min only. The calibration curve was found to be linear over the concentration range of 0.40–500 ng/mL. The intra- and inter-day precision value was ≤10.6% and the accuracy ranged from 90.9-108.9%. In addition, all the validation results were within general assay acceptability criteria according to guidelines of bio-analytical method validation. CONCLUSION: A selective and sensitive UHPLC-MS/MS method was developed and validated for the determination of linifanib in rat plasma for the first time. The developed method is simple, sensitive and rapid in terms of chromatographic separation and sample preparation and was successfully applied in a pilot pharmacokinetic study in rats. |
format | Online Article Text |
id | pubmed-3932137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39321372014-02-23 Simple, sensitive and rapid determination of linifanib (ABT-869), a novel tyrosine kinase inhibitor in rat plasma by UHPLC-MS/MS Iqbal, Muzaffar Ezzeldin, Essam Wani, Tanveer A Khalil, Nasr Y Chem Cent J Research Article BACKGROUND: Linifanib (ABT-869) is an orally active receptor tyrosine kinase inhibitor, which simultaneously inhibits vascular endothelial and platelet derived growth factor receptor. The aim of the present study was to develop an UHPLC-MS/MS method for the quantification of linifanib in rat plasma to support the pharmacokinetic and toxicokinetic studies. RESULTS: Linifanib was separated on Acquity UPLC BEH™ C(18) column (50 × 2.1 mm, i.d. 1.7 μm) using acetonitrile-10 mM ammonium acetate (60:40, v/v) as an isocratic mobile phase at a flow rate of 0.3 mL/min with sunitinib as internal standard (IS). Detection was performed on tandem mass spectrometer using electrospray ionization source in positive mode by multiple reaction monitoring. The monitored transitions were set at m/z 376.05 > 250.97 for linifanib and m/z 399.12 >283.02 for IS, respectively. Both linifanib and IS were eluted at 0.68 and 0.44 min, respectively with a total run time of 2.0 min only. The calibration curve was found to be linear over the concentration range of 0.40–500 ng/mL. The intra- and inter-day precision value was ≤10.6% and the accuracy ranged from 90.9-108.9%. In addition, all the validation results were within general assay acceptability criteria according to guidelines of bio-analytical method validation. CONCLUSION: A selective and sensitive UHPLC-MS/MS method was developed and validated for the determination of linifanib in rat plasma for the first time. The developed method is simple, sensitive and rapid in terms of chromatographic separation and sample preparation and was successfully applied in a pilot pharmacokinetic study in rats. BioMed Central 2014-02-17 /pmc/articles/PMC3932137/ /pubmed/24533632 http://dx.doi.org/10.1186/1752-153X-8-13 Text en Copyright © 2014 Iqbal et al.; licensee Chemistry Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Iqbal, Muzaffar Ezzeldin, Essam Wani, Tanveer A Khalil, Nasr Y Simple, sensitive and rapid determination of linifanib (ABT-869), a novel tyrosine kinase inhibitor in rat plasma by UHPLC-MS/MS |
title | Simple, sensitive and rapid determination of linifanib (ABT-869), a novel tyrosine kinase inhibitor in rat plasma by UHPLC-MS/MS |
title_full | Simple, sensitive and rapid determination of linifanib (ABT-869), a novel tyrosine kinase inhibitor in rat plasma by UHPLC-MS/MS |
title_fullStr | Simple, sensitive and rapid determination of linifanib (ABT-869), a novel tyrosine kinase inhibitor in rat plasma by UHPLC-MS/MS |
title_full_unstemmed | Simple, sensitive and rapid determination of linifanib (ABT-869), a novel tyrosine kinase inhibitor in rat plasma by UHPLC-MS/MS |
title_short | Simple, sensitive and rapid determination of linifanib (ABT-869), a novel tyrosine kinase inhibitor in rat plasma by UHPLC-MS/MS |
title_sort | simple, sensitive and rapid determination of linifanib (abt-869), a novel tyrosine kinase inhibitor in rat plasma by uhplc-ms/ms |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932137/ https://www.ncbi.nlm.nih.gov/pubmed/24533632 http://dx.doi.org/10.1186/1752-153X-8-13 |
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