Cargando…

In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method

In the current research experiment, a sensitive, precise and rapid bioanalytical approach involving the detection of fedratinib concentrations in rat plasma by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique was optimized and established, and it was employed t...

Descripción completa

Detalles Bibliográficos
Autores principales: Tang, Congrong, Niu, Xiaohui, Shi, Lu, Zhu, Huidan, Lin, Guanyang, Xu, Ren-ai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892954/
https://www.ncbi.nlm.nih.gov/pubmed/33613287
http://dx.doi.org/10.3389/fphar.2020.626897
_version_ 1783652960679493632
author Tang, Congrong
Niu, Xiaohui
Shi, Lu
Zhu, Huidan
Lin, Guanyang
Xu, Ren-ai
author_facet Tang, Congrong
Niu, Xiaohui
Shi, Lu
Zhu, Huidan
Lin, Guanyang
Xu, Ren-ai
author_sort Tang, Congrong
collection PubMed
description In the current research experiment, a sensitive, precise and rapid bioanalytical approach involving the detection of fedratinib concentrations in rat plasma by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique was optimized and established, and it was employed to describe the changes of fedratinib concentrations after oral treatment with various antifungal drugs (isavuconazole, posaconazole, fluconazole and itraconazole). An Acquity UPLC BEH reverse-phase C18 column (2.1 mm × 50 mm, 1.7 μm) was used for chromatographic separation of fedratinib and bosutinib (as internal standard (IS) in our study) under a linear gradient elution of the mobile phase, which was composed of solution A (acetonitrile) and solution B (water with 0.1% formic acid), along with 0.40 ml/min flow rate. The analyte and internal standard were measured with electrospray ion source in positive ion mode on a XEVO TQS triple quadrupole tandem mass spectrometer. The newly developed UPLC-MS/MS assay displayed enough linearity within the concentration range of 0.5–500 ng/ml for calibration curve. The intra- and inter-day of precision and accuracy were evaluated and validated to meet the requirements for the guidelines of bioanalytical assay. In addition, the findings of matrix effect, recovery, and stability were all within the acceptable limits. The new UPLC-MS/MS method was also successfully applied to characterize the pharmacokinetic changes of fedratinib in rats in the present of different antifungal drugs (such as isavuconazole, posaconazole, fluconazole and itraconazole). It turned out that fluconazole resulted in a prominent inhibitory effect on fedratinib metabolism in rats, followed by treatment with itraconazole and isavuconazole. Therefore, the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors may occur.
format Online
Article
Text
id pubmed-7892954
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-78929542021-02-20 In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method Tang, Congrong Niu, Xiaohui Shi, Lu Zhu, Huidan Lin, Guanyang Xu, Ren-ai Front Pharmacol Pharmacology In the current research experiment, a sensitive, precise and rapid bioanalytical approach involving the detection of fedratinib concentrations in rat plasma by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique was optimized and established, and it was employed to describe the changes of fedratinib concentrations after oral treatment with various antifungal drugs (isavuconazole, posaconazole, fluconazole and itraconazole). An Acquity UPLC BEH reverse-phase C18 column (2.1 mm × 50 mm, 1.7 μm) was used for chromatographic separation of fedratinib and bosutinib (as internal standard (IS) in our study) under a linear gradient elution of the mobile phase, which was composed of solution A (acetonitrile) and solution B (water with 0.1% formic acid), along with 0.40 ml/min flow rate. The analyte and internal standard were measured with electrospray ion source in positive ion mode on a XEVO TQS triple quadrupole tandem mass spectrometer. The newly developed UPLC-MS/MS assay displayed enough linearity within the concentration range of 0.5–500 ng/ml for calibration curve. The intra- and inter-day of precision and accuracy were evaluated and validated to meet the requirements for the guidelines of bioanalytical assay. In addition, the findings of matrix effect, recovery, and stability were all within the acceptable limits. The new UPLC-MS/MS method was also successfully applied to characterize the pharmacokinetic changes of fedratinib in rats in the present of different antifungal drugs (such as isavuconazole, posaconazole, fluconazole and itraconazole). It turned out that fluconazole resulted in a prominent inhibitory effect on fedratinib metabolism in rats, followed by treatment with itraconazole and isavuconazole. Therefore, the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors may occur. Frontiers Media S.A. 2021-02-05 /pmc/articles/PMC7892954/ /pubmed/33613287 http://dx.doi.org/10.3389/fphar.2020.626897 Text en Copyright © 2021 Tang, Niu, Shi, Zhu, Lin and Xu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/) . 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
Tang, Congrong
Niu, Xiaohui
Shi, Lu
Zhu, Huidan
Lin, Guanyang
Xu, Ren-ai
In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method
title In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method
title_full In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method
title_fullStr In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method
title_full_unstemmed In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method
title_short In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method
title_sort in vivo pharmacokinetic drug-drug interaction studies between fedratinib and antifungal agents based on a newly developed and validated uplc/ms-ms method
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892954/
https://www.ncbi.nlm.nih.gov/pubmed/33613287
http://dx.doi.org/10.3389/fphar.2020.626897
work_keys_str_mv AT tangcongrong invivopharmacokineticdrugdruginteractionstudiesbetweenfedratinibandantifungalagentsbasedonanewlydevelopedandvalidateduplcmsmsmethod
AT niuxiaohui invivopharmacokineticdrugdruginteractionstudiesbetweenfedratinibandantifungalagentsbasedonanewlydevelopedandvalidateduplcmsmsmethod
AT shilu invivopharmacokineticdrugdruginteractionstudiesbetweenfedratinibandantifungalagentsbasedonanewlydevelopedandvalidateduplcmsmsmethod
AT zhuhuidan invivopharmacokineticdrugdruginteractionstudiesbetweenfedratinibandantifungalagentsbasedonanewlydevelopedandvalidateduplcmsmsmethod
AT linguanyang invivopharmacokineticdrugdruginteractionstudiesbetweenfedratinibandantifungalagentsbasedonanewlydevelopedandvalidateduplcmsmsmethod
AT xurenai invivopharmacokineticdrugdruginteractionstudiesbetweenfedratinibandantifungalagentsbasedonanewlydevelopedandvalidateduplcmsmsmethod