Improving sensitivity of antimicrobial drug nitrofurazone detection in food and biological samples based on nanostructured anatase-titania sheathed reduced graphene oxide.

In this study, we have prepared anatase titanium (IV) oxide warped reduced graphene oxide nanocomposites (TiO2-rGO NC) using ultrasonic methodology. The morphology of the TiO2-rGO NC was studied using FESEM and TEM. In addition, XRD, Raman, thermogravimetric analysis (TGA) and XPS are used to analyze the crystallinity and chemical composition of the TiO2-rGO NC. We have also investigated the electrochemical behavior of the as-prepared NCs with electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and different pulse voltammetry techniques (DPV). The TiO2-rGO NC modified electrode shows the lower charge transfer resistance (R ct ) of 62.87 Ω. Next, the glassy carbon electrode (GCE) was modified with sonochemically prepared TiO2-rGO NC and used to determine the electrocatalytic reduction of nitrofurazone (NTF). Thus, the proposed sensor established the wider covering range (WCR) of 0.01 to 380 µM and an excellent detection limit of 2.28 nM. Finally, the TiO2-rGO NC/GCE was applied to determine the NTF in real samples, including crayfish and human blood serum samples, which acquired good found and recovery values.

A new medium-throughput screening design approach for the development of hydroxymethylnitrofurazone (NFOH) nanostructured lipid carrier for treating leishmaniasis.

Hydroxymethilnitrofurazone (NFOH) is a nitrofurazone derivative and has potential use in treating leishmaniasis. However, due to low water solubility and bioavailability, NFOH has failed in in vivo tests. Nanostructured lipid carrier (NLC) is an alternative to overcome these limitations by improving pharmacokinetics and modifying drug delivery. This work is focused on developing a novel NFOH-loaded NLC (NLC-NFOH) using a D-optimal mixture statistical design and high-pressure homogenization, for oral administration to treat leishmaniasis. The optimized NLC-NFOH consisted of Mygliol® 840, Gelucire® 50/13, and Precirol® ATO 5 as lipids. These lipids were selected using a rapid methodology Technobis Crystal 16 T M, microscopy, and DSC. Different tools for selecting lipids provided relevant scientific knowledge for the development of the NLC. NLC-NFOH presented a z-average of 198.6 ±â€¯5.4 nm, PDI of 0.11 ±â€¯0.01, and zeta potential of -13.7 ±â€¯0.7 mV. A preliminary in vivo assay was performed by oral administration of NLC-NFOH (2.8 mg/kg) in one healthy male Wistar rat (341 g) by gavage. Blood from the carotid vein was collected, and the sample was analyzed by HPLC. The plasma concentration of NFOH after 5 h of oral administration was 0.22 µg/mL. This same concentration was previously found using free NFOH in the DMSO solution (200 mg/kg), which is an almost 100-fold higher dose. This study allowed a design space development approach of the first NLC-NFOH with the potential to treat leishmaniasis orally.

Pharmacokinetics of hydroxymethylnitrofurazone, a promising new prodrug for Chagas' disease treatment.

Hydroxymethylnitrofurazone (NFOH) is a trypanocidal prodrug of nitrofurazone (NF), devoid of mutagenic toxicity. The purpose of this work was to study the chemical conversion of NFOH into NF in sodium acetate buffer (pH 1.2 and 7.4) and in human plasma and to determine preclinical pharmacokinetic parameters in rats. At pH 1.2, the NFOH was totally transformed into NF, the parent drug, after 48 h, while at pH 7.4, after the same period, the hydrolysis rate was 20%. In human plasma, 50% of NFOH was hydrolyzed after 24 h. In the investigation of kinetic disposition, the concentration of drug in serum versus time curve was used to calculate the pharmacokinetic parameters after a single-dose regimen. NFOH showed a time to maximum concentration of drug in serum (Tmax) as 1 h, suggesting faster absorption than NF (4 h). The most important results observed were the volume of distribution (V) of NFOH through the tissues, which showed a rate that is 20-fold higher (337.5 liters/kg of body weight) than that of NF (17.64 liters/kg), and the concentration of NF obtained by in vivo metabolism of NFOH, which was about four times lower (maximum concentration of drug in serum [Cmax] = 0.83 µg/ml; area under the concentration-time curve from 0 to 12 h [AUC0-12] = 5.683 µg/ml · h) than observed for administered NF (Cmax = 2.78 µg/ml; AUC0-12 = 54.49 µg/ml · h). These findings can explain the superior activity and lower toxicity of the prodrug NFOH in relation to its parent drug and confirm NFOH as a promising anti-Chagas' disease drug candidate.

Quantitation of nitrofurantoin in human plasma by liquid chromatography tandem mass spectrometry.

A reliable, selective and sensitive LC-MS/MS assay has been proposed for the determination of nitrofurantoin in human plasma. The analyte and nitrofurazone were extracted from 100 µL of human plasma via SPE on Strata-X 33 µm extraction cartridges. Chromatography was done on a BDS Hypersil C18 (100 mm × 4.6 mm, 5 µm) column under isocratic conditions. Quantitation was done using the multiple reaction monitoring (MRM) mode for deprotonated precursor to product ion transitions of nitrofurantoin (m/z 237.0 → 151.8) and nitrofurazone (m/z 197.0 → 123.9). The limit of detection and the lowest limit of quantitation of the method were 0.25 ng mL-1 and 5.00 ng mL-1, respectively, with a linear dynamic range of 5.00-1500 ng mL-1 for nitrofurantoin. The intra- -batch and inter-batch precision (RSD, %) was ≤ 5.8 %, while the mean extraction recovery was > 92 %. The method was successfully applied to a bioequivalence study of a 100 mg nitrofurantoin capsule formulation in 36 healthy subjects.