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Validated DBS method for filgotinib quantitation in rat dried blood spots and its application to a pharmacokinetic study in rats

Filgotinib is a selective JAK1 (Janus kinase) inhibitor, showed efficacy in patients suffering from moderate-to-severe rheumatoid arthritis. In this paper, we present the data on the development and validation of a sensitive, selective and high-throughput LC-MS/MS (liquid chromatography with tandem...

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Autores principales: Dixit, Abhishek, Kiran, Vinay, Gabani, Bhavesh Babulal, Mullangi, Ramesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Association of Physical Chemists 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915582/
https://www.ncbi.nlm.nih.gov/pubmed/35300367
http://dx.doi.org/10.5599/admet.796
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author Dixit, Abhishek
Kiran, Vinay
Gabani, Bhavesh Babulal
Mullangi, Ramesh
author_facet Dixit, Abhishek
Kiran, Vinay
Gabani, Bhavesh Babulal
Mullangi, Ramesh
author_sort Dixit, Abhishek
collection PubMed
description Filgotinib is a selective JAK1 (Janus kinase) inhibitor, showed efficacy in patients suffering from moderate-to-severe rheumatoid arthritis. In this paper, we present the data on the development and validation of a sensitive, selective and high-throughput LC-MS/MS (liquid chromatography with tandem mass spectrometry) method for the quantitation of filgotinib from rat dried blood spot (DBS) cards. To the DBS disc cards, 0.2% formic acid enriched with internal standard (IS) was added and sonicated. Thereafter the extraction of filgotinib and the IS (tofacitinib) was accomplished using ethyl acetate as an extraction solvent. The resolution of filgotinib and the IS was achieved on a Gemini C(18) column with an isocratic mobile phase, which is a mixture of 0.2% formic acid:acetonitrile (20:80, v/v) at a flow-rate of 0.9 mL/min. The total run time was 2.90 min and the retention time of filgotinib and the IS was ~1.31 and 0.89 min, respectively. Filgotinib and the IS were analyzed using positive ion scan mode and parent-daughter mass to charge ion (m/z) transition of 426.3→291.3 and m/z 313.2→149.2, respectively, for quantitation. The calibration range was 1.37-1937 ng/mL. No matrix effect and carry over were observed. All the validation parameters met the acceptance criteria. The validated method has been applied to a pharmacokinetic study in rats. A good correlation between DBS and plasma concentrations for filgotinib was observed.
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spelling pubmed-89155822022-03-16 Validated DBS method for filgotinib quantitation in rat dried blood spots and its application to a pharmacokinetic study in rats Dixit, Abhishek Kiran, Vinay Gabani, Bhavesh Babulal Mullangi, Ramesh ADMET DMPK Original Scientific Papers Filgotinib is a selective JAK1 (Janus kinase) inhibitor, showed efficacy in patients suffering from moderate-to-severe rheumatoid arthritis. In this paper, we present the data on the development and validation of a sensitive, selective and high-throughput LC-MS/MS (liquid chromatography with tandem mass spectrometry) method for the quantitation of filgotinib from rat dried blood spot (DBS) cards. To the DBS disc cards, 0.2% formic acid enriched with internal standard (IS) was added and sonicated. Thereafter the extraction of filgotinib and the IS (tofacitinib) was accomplished using ethyl acetate as an extraction solvent. The resolution of filgotinib and the IS was achieved on a Gemini C(18) column with an isocratic mobile phase, which is a mixture of 0.2% formic acid:acetonitrile (20:80, v/v) at a flow-rate of 0.9 mL/min. The total run time was 2.90 min and the retention time of filgotinib and the IS was ~1.31 and 0.89 min, respectively. Filgotinib and the IS were analyzed using positive ion scan mode and parent-daughter mass to charge ion (m/z) transition of 426.3→291.3 and m/z 313.2→149.2, respectively, for quantitation. The calibration range was 1.37-1937 ng/mL. No matrix effect and carry over were observed. All the validation parameters met the acceptance criteria. The validated method has been applied to a pharmacokinetic study in rats. A good correlation between DBS and plasma concentrations for filgotinib was observed. International Association of Physical Chemists 2020-05-06 /pmc/articles/PMC8915582/ /pubmed/35300367 http://dx.doi.org/10.5599/admet.796 Text en Copyright © 2020 by the authors. https://creativecommons.org/licenses/by/4.0/This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Original Scientific Papers
Dixit, Abhishek
Kiran, Vinay
Gabani, Bhavesh Babulal
Mullangi, Ramesh
Validated DBS method for filgotinib quantitation in rat dried blood spots and its application to a pharmacokinetic study in rats
title Validated DBS method for filgotinib quantitation in rat dried blood spots and its application to a pharmacokinetic study in rats
title_full Validated DBS method for filgotinib quantitation in rat dried blood spots and its application to a pharmacokinetic study in rats
title_fullStr Validated DBS method for filgotinib quantitation in rat dried blood spots and its application to a pharmacokinetic study in rats
title_full_unstemmed Validated DBS method for filgotinib quantitation in rat dried blood spots and its application to a pharmacokinetic study in rats
title_short Validated DBS method for filgotinib quantitation in rat dried blood spots and its application to a pharmacokinetic study in rats
title_sort validated dbs method for filgotinib quantitation in rat dried blood spots and its application to a pharmacokinetic study in rats
topic Original Scientific Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915582/
https://www.ncbi.nlm.nih.gov/pubmed/35300367
http://dx.doi.org/10.5599/admet.796
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