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Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice
Nifuroxazide (NAZ), a nitrofuran derivative used to treat diarrhea, has been recently shown to possess anticancer activity. However, its pharmacokinetic profile is poorly known. The pharmacokinetic profile of NAZ was thus investigated in mice using a newly developed method based on high-performance...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608191/ https://www.ncbi.nlm.nih.gov/pubmed/36297506 http://dx.doi.org/10.3390/pharmaceutics14102071 |
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author | Ceruti, Tommaso D’Alessandris, Quintino Giorgio Frapolli, Roberta Gopalakrishnan, Jay Buccarelli, Mariachiara Meroni, Marina Lauretti, Liverana Ricci-Vitiani, Lucia Pallini, Roberto Zucchetti, Massimo |
author_facet | Ceruti, Tommaso D’Alessandris, Quintino Giorgio Frapolli, Roberta Gopalakrishnan, Jay Buccarelli, Mariachiara Meroni, Marina Lauretti, Liverana Ricci-Vitiani, Lucia Pallini, Roberto Zucchetti, Massimo |
author_sort | Ceruti, Tommaso |
collection | PubMed |
description | Nifuroxazide (NAZ), a nitrofuran derivative used to treat diarrhea, has been recently shown to possess anticancer activity. However, its pharmacokinetic profile is poorly known. The pharmacokinetic profile of NAZ was thus investigated in mice using a newly developed method based on high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS). We determined the concentrations of NAZ in the plasma and brain tissue of mice treated with the drug. The method proved to be specific, reproducible, precise, and accurate. It also demonstrated high sensitivity, reaching an LOQ in the order of ppb for both matrices, using samples of 100 µL or 0.2 g. The new HPLC–MS/MS assay was successfully applied to study the pharmacokinetics of NAZ after chronic intraperitoneal administration in mice at a dose of 30 mg/kg. One hour after treatment, plasma concentrations of NAZ were in the range of 336–2640 ng/mL. Moreover, unlike the brains of healthy mice or those with healed mechanical injuries, we found that NAZ was able to cross the injured blood–brain barrier of tumor-infiltrated brains. Thus, following i.p. administration, NAZ reaches systemic levels suitable for testing its efficacy in preclinical models of glioblastoma. Overall, these pharmacokinetic data provide robust evidence supporting the repositioning of NAZ as an antitumor drug. |
format | Online Article Text |
id | pubmed-9608191 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96081912022-10-28 Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice Ceruti, Tommaso D’Alessandris, Quintino Giorgio Frapolli, Roberta Gopalakrishnan, Jay Buccarelli, Mariachiara Meroni, Marina Lauretti, Liverana Ricci-Vitiani, Lucia Pallini, Roberto Zucchetti, Massimo Pharmaceutics Article Nifuroxazide (NAZ), a nitrofuran derivative used to treat diarrhea, has been recently shown to possess anticancer activity. However, its pharmacokinetic profile is poorly known. The pharmacokinetic profile of NAZ was thus investigated in mice using a newly developed method based on high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS). We determined the concentrations of NAZ in the plasma and brain tissue of mice treated with the drug. The method proved to be specific, reproducible, precise, and accurate. It also demonstrated high sensitivity, reaching an LOQ in the order of ppb for both matrices, using samples of 100 µL or 0.2 g. The new HPLC–MS/MS assay was successfully applied to study the pharmacokinetics of NAZ after chronic intraperitoneal administration in mice at a dose of 30 mg/kg. One hour after treatment, plasma concentrations of NAZ were in the range of 336–2640 ng/mL. Moreover, unlike the brains of healthy mice or those with healed mechanical injuries, we found that NAZ was able to cross the injured blood–brain barrier of tumor-infiltrated brains. Thus, following i.p. administration, NAZ reaches systemic levels suitable for testing its efficacy in preclinical models of glioblastoma. Overall, these pharmacokinetic data provide robust evidence supporting the repositioning of NAZ as an antitumor drug. MDPI 2022-09-28 /pmc/articles/PMC9608191/ /pubmed/36297506 http://dx.doi.org/10.3390/pharmaceutics14102071 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ceruti, Tommaso D’Alessandris, Quintino Giorgio Frapolli, Roberta Gopalakrishnan, Jay Buccarelli, Mariachiara Meroni, Marina Lauretti, Liverana Ricci-Vitiani, Lucia Pallini, Roberto Zucchetti, Massimo Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice |
title | Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice |
title_full | Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice |
title_fullStr | Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice |
title_full_unstemmed | Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice |
title_short | Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice |
title_sort | development and validation of a hplc–ms/ms method to measure nifuroxazide and its application in healthy and glioblastoma-bearing mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608191/ https://www.ncbi.nlm.nih.gov/pubmed/36297506 http://dx.doi.org/10.3390/pharmaceutics14102071 |
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