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...
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MDPI AG
2022-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/10/2071 |
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| author | Tommaso Ceruti Quintino Giorgio D’Alessandris Roberta Frapolli Jay Gopalakrishnan Mariachiara Buccarelli Marina Meroni Liverana Lauretti Lucia Ricci-Vitiani Roberto Pallini Massimo Zucchetti |
| author_facet | Tommaso Ceruti Quintino Giorgio D’Alessandris Roberta Frapolli Jay Gopalakrishnan Mariachiara Buccarelli Marina Meroni Liverana Lauretti Lucia Ricci-Vitiani Roberto Pallini Massimo Zucchetti |
| author_sort | Tommaso Ceruti |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T19:35:13Z |
| format | Article |
| id | doaj.art-0bca9f8bea374fa2ac895476d7b94cbf |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T19:35:13Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-0bca9f8bea374fa2ac895476d7b94cbf2023-11-24T01:55:15ZengMDPI AGPharmaceutics1999-49232022-09-011410207110.3390/pharmaceutics14102071Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing MiceTommaso Ceruti0Quintino Giorgio D’Alessandris1Roberta Frapolli2Jay Gopalakrishnan3Mariachiara Buccarelli4Marina Meroni5Liverana Lauretti6Lucia Ricci-Vitiani7Roberto Pallini8Massimo Zucchetti9Laboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, ItalyDepartment of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, ItalyLaboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, ItalyInstitute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Moorenstr. 5, 40225 Düsseldorf, GermanyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyLaboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, ItalyDepartment of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, ItalyDepartment of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, ItalyLaboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, ItalyNifuroxazide (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.https://www.mdpi.com/1999-4923/14/10/2071nifuroxazideliquid chromatography–tandem mass spectrometry techniquepharmacokineticsmurine modeldrug repositioning |
| spellingShingle | Tommaso Ceruti Quintino Giorgio D’Alessandris Roberta Frapolli Jay Gopalakrishnan Mariachiara Buccarelli Marina Meroni Liverana Lauretti Lucia Ricci-Vitiani Roberto Pallini Massimo Zucchetti Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice Pharmaceutics nifuroxazide liquid chromatography–tandem mass spectrometry technique pharmacokinetics murine model drug repositioning |
| 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 | nifuroxazide liquid chromatography–tandem mass spectrometry technique pharmacokinetics murine model drug repositioning |
| url | https://www.mdpi.com/1999-4923/14/10/2071 |
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