TY - JOUR
T1 - Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice
AU - Ceruti, Tommaso
AU - D'Alessandris, Quintino Giorgio
AU - Frapolli, Roberta
AU - Gopalakrishnan, Jay
AU - Buccarelli, Mariachiara
AU - Meroni, Marina
AU - Lauretti, Liverana
AU - Ricci-Vitiani, Lucia
AU - Pallini, Roberto
AU - Zucchetti, Massimo
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - drug repositioning
KW - liquid chromatography–tandem mass spectrometry technique
KW - murine model
KW - nifuroxazide
KW - pharmacokinetics
KW - drug repositioning
KW - liquid chromatography–tandem mass spectrometry technique
KW - murine model
KW - nifuroxazide
KW - pharmacokinetics
UR - http://hdl.handle.net/10807/218986
U2 - 10.3390/pharmaceutics14102071
DO - 10.3390/pharmaceutics14102071
M3 - Article
SN - 1999-4923
VL - 14
SP - N/A-N/A
JO - Pharmaceutics
JF - Pharmaceutics
ER -