Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ceruti, Tommaso, D’Alessandris, Quintino Giorgio, Frapolli, Roberta, Gopalakrishnan, Jay, Buccarelli, Mariachiara, Meroni, Marina, Lauretti, Liverana, Ricci-Vitiani, Lucia, Pallini, Roberto, Zucchetti, Massimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784818720113164288
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
work_keys_str_mv AT cerutitommaso developmentandvalidationofahplcmsmsmethodtomeasurenifuroxazideanditsapplicationinhealthyandglioblastomabearingmice
AT dalessandrisquintinogiorgio developmentandvalidationofahplcmsmsmethodtomeasurenifuroxazideanditsapplicationinhealthyandglioblastomabearingmice
AT frapolliroberta developmentandvalidationofahplcmsmsmethodtomeasurenifuroxazideanditsapplicationinhealthyandglioblastomabearingmice
AT gopalakrishnanjay developmentandvalidationofahplcmsmsmethodtomeasurenifuroxazideanditsapplicationinhealthyandglioblastomabearingmice
AT buccarellimariachiara developmentandvalidationofahplcmsmsmethodtomeasurenifuroxazideanditsapplicationinhealthyandglioblastomabearingmice
AT meronimarina developmentandvalidationofahplcmsmsmethodtomeasurenifuroxazideanditsapplicationinhealthyandglioblastomabearingmice
AT laurettiliverana developmentandvalidationofahplcmsmsmethodtomeasurenifuroxazideanditsapplicationinhealthyandglioblastomabearingmice
AT riccivitianilucia developmentandvalidationofahplcmsmsmethodtomeasurenifuroxazideanditsapplicationinhealthyandglioblastomabearingmice
AT palliniroberto developmentandvalidationofahplcmsmsmethodtomeasurenifuroxazideanditsapplicationinhealthyandglioblastomabearingmice
AT zucchettimassimo developmentandvalidationofahplcmsmsmethodtomeasurenifuroxazideanditsapplicationinhealthyandglioblastomabearingmice