Ultrasound supported synthesis of tantalum carbide integrated functionalized carbon composite for the voltammetric determination of the antibacterial drug nitrofurantoin in pharmaceutical samples.

The synthesis and fabrication of oval-shaped tantalum carbide (Ta-C) integrated functionalized-multiwalled carbon nanotube (Ta-C/f-MWCNT) as an electrocatalyst for the electrochemical determination of nitrofurantoin (NFT) is described. The Ta-C/f-MWCNT composite was prepared using the soft-template method followed by the ultrasonication process. The as-prepared Ta-C/f-MWCNT composite was characterized using powder X-ray diffraction (XRD), Raman spectroscopy, field emission scanning electron microscopy (FESEM), scanning transmission electron microscopy (STEM), and X-ray photoelectron spectroscopy (XPS) analysis. The electrochemical properties of Ta-C/f-MWCNT were investigated by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and linear sweep voltammetry (LSV). The Ta-C/f-MWCNT-modified glassy carbon electrode (Ta-C/f-MWCNT/GCE) was successfully utilized as an active electrocatalyst for the detection of NFT in the presence of 0.384 mM NFT containing 0.05 M phosphate buffer (pH 7) at a scan rate of 50 mV/s. The Ta-C/f-MWCNT/GCE exhibited a wide linear response range (0.04-1047 µM) and a low detection limit (0.0011 µM). Further, the Ta-C/f-MWCNT/GCE showed appreciable results for repeatability, reproducibility, and long-term cyclic stability towards NFT sensing. The Ta-C/f-MWCNT/GCE was applied to real sample analysis such as a commercial tablet and human urine samples. The Ta-C/f-MWCNT/GCE exhibited good recovery values for the tablet (105 to 115%) and urine (101-107%) samples. The above electrochemical results suggest that the Ta-C/f-MWCNT is a promising electrocatalyst for the electrochemical sensing of NFT drug. Graphical abstract .

Development and validation of a fast and sensitive UHPLC-DAD assay for the quantification of nitrofurantoin in plasma and urine.

Nitrofurantoin is an antimicrobial drug that has been used in the treatment of lower urinary tract infections for more than 50 years. Despite its long use, surprisingly little is known of the pharmacokinetics of nitrofurantoin, whereas this is essential to optimize patient treatment. We developed a novel analytical method for the quantification of nitrofurantoin in plasma and urine using ultra-high performance liquid chromatography and diode array detection to allow pharmacokinetic studies in these two matrices. The sample preparation method consisted of protein precipitation for plasma and liquid-liquid extraction for urine. 100 µL was needed for the sample preparation. Furazolidone was used as internal standard. Gradient chromatographic separation was performed on a HSS-T3 column. UV detection was performed at a wavelength of 369 nm. The analysis time was 5 min. The method was successfully validated according to the FDA-guidelines (2018). Linearity was confirmed over a concentration range from 50 to 1250 µg/L in plasma and from 4 to 200 mg/L in urine (r2 > 0.95). Validation results of five QC concentrations for plasma and urine, respectively, are for within-day accuracy <± 13% in both matrices, for between-day accuracy <± 7% and <± 9%, for within-day precision <10% and <4% and for between-day precision <10% and <5%. Plasma samples are stable for seven days at 4 °C, and for 2 years at -20 °C and-80 °C. Urine samples are stable for at least seven days at 4 °C and at room temperature and for 2 years at -20 °C andat -80 °C, except from the lower concentrated samples, which are only stable at -80 °C. All samples were kept from daylight using amber colored glassware. The presented method meets all validation requirements and was successfully used in a clinical study where the pharmacokinetics of nitrofurantoin were investigated in healthy volunteers. The easy sample preparation method and the short analysis time make this method suitable for use during routine clinical practice to study the pharmacokinetics of nitrofurantoin.

Determination of nitrofurantoin drug in pharmaceutical formulation and biological fluids by square-wave cathodic adsorptive stripping voltammetry.

Nitrofurnation is an antibacterial drug. It is used in the treatment of initial or recurrent urinary tract infections caused by susceptible organisms. The cyclic voltammogram of the drug in Britton-Robinson buffers (pH 2-11) exhibited a single well-defined cathodic peak at the hanging mercury drop electrode, that due to the reduction of its nitro group to the amine stage. A fully validated, sensitive, and reproducible developed procedure was described for determination of the drug in bulk form, pharmaceutical formulation, human serum and human urine using, square-wave cathodic adsorptive stripping voltammetry. The optimal experimental parameters for the drug assay were: accumulation potential = -0.4 V (vs. Ag/AgCl/ KCl(s)), accumulation time = 40 s, frequency = 120 Hz, pulse amplitude = 50 mV and scan increment = 10 mV in Britton-Robinson buffer (pH 10). A mean percentage recovery of 100.68 +/- 0.17 (n = 5) and a detection limit of 1.32 x 10(-10) M of bulk drug were achieved. Applicability to assay of the drug in pharmaceutical formulation, human serum and human urine was studied and illustrated. The mean percentage recoveries were found as: 101.49 +/- 0.65, 103.94 +/- 0.73 and 101.98 +/- 0.52 (n = 5) in pharmaceutical formulation, human serum and human urine, respectively. Detection limits of 2.86 x 10(-10) M and 5.77 x 10(-10) M nitrofurantoin were achieved in human serum and urine, respectively.

N-allyl-4-(N-2'-hydroxyethyl)amino-1,8-naphthalimide as a fluorophore for optical chemosensing of nitrofurantoin.

N-Allyl-4-(N-2'-hydroxyethyl)amino-1,8-naphthalimide (AHEAN), a naphthalimide derivative, was synthesized as a new fluorophore for optical chemical sensor preparation. To prevent leakage of the fluorophore, AHEAN was photo-copolymerized with 2-hydroxypropyl methacrylate on a glass surface treated with a silanizing agent. An optical chemical sensor based on AHEAN can be utilized for nitrofurantoin assay based on fluorescence quenching. The sensor shows sufficient repeatability, selectivity and a fast response of less than 30 s. Nitrofurantoin can be determined in the range between 1.00 x 10(-6) and 1.00 x 10(-3) mol l(-1) with a detection limit of 4.8 x 10(-7) mol l(-1). Most commonly co-existing drug substances and ions do not interfere with the nitrofurantoin assay. The sensor was applied to the analysis of pharmaceutical and urine samples.

A new in vitro/in vivo kinetic correlation method for nitrofurantoin matrix tablet formulations.

The kinetic distributions of in vitro percentage release and in vivo percentage urinary excretion rates of nitrofurantoin from matrix tablets were plotted using a kinetic program. In vitro release rates were determined using the USP paddle and half-change methods. Urinary excretion curves of the drug were characterized by means of the statistical moments. The individual linear correlations between each in vitro and in vivo kinetic distribution were established, and regression equations were calculated. The application results of the best correlations obtained were evaluated according to in vivo results. A reversed kinetic procedure was applied for transformation of the correlated kinetic values to the drug percentage release rates. The modified Langenbucher kinetic showed excellent linear correlation (r = .9985). The method that is proposed in this study, the kinetic correlation program, is simple, independent of time, and suggests that it is possible to use kinetic distributions in the in vitro/in vivo correlation. This study also suggests using kinetic correlation to investigate the suitability of the in vitro dissolution methods with the in vivo drug dissolution.

Sensitive determination of nitrofurantoin in human plasma and urine by high-performance liquid chromatography.

A highly sensitive and selective HPLC method was developed and validated for the determination of nitrofurantoin in human plasma and urine. The method involves the liquid-liquid extraction of drug and internal standard from plasma with ethyl acetate followed by evaporation and reconstitution in mobile phase. Urine samples were simply diluted with purified water. UV detection was done at 370 nm. The limit of quantification for nitrofurantoin in plasma was 0.010 micrograms/ml. In urine nitrofurantoin could be quantified down to 0.380 microgram/ml. Linearity was proven over the whole calibration range in plasma (2.48-0.0100 microgram/ml) as well as in urine (187 micrograms/ml-0.380 microgram/ml). The method was validated according to Good Laboratory Practice guidelines and its suitability was demonstrated by analysis of samples from a pharmacokinetic study.

In vivo/in vitro correlations of nitrofurantoin matrix tablet formulations.

In our recent study, a new sustained release dosage form of nitrofurantoin (nft) as matrix tablets by 2(2) factorial design has been prepared by using different drug:polymer ratios. The effect of the polyvinylpyrolidone contents of nft matrix tablets on dissolution rate and bioavailability of the drug have been evaluated. The ideal formulation which fitted at USP XXII dissolution norms was tested by in vivo experiments. The satisfactory correlation was also obtained between the in vivo and the in vitro results. This study suggested that the amounts of nft excreted in urine can be calculated by using in vitro dissolution results and sampling time.

[On-line monitoring of nitrofurantoin in urine of rabbit by a flow-injection system with a fiber-optic chemical sensor].

A flow-injection system for monitoring of nitrofurantoin (NFT) in rabbit urine that makes use of a kind of fiber-optic chemical sensor is presented. The NFT-sensitive optrode was combined with a membrane onto which was immobilized pyrenebutyric acid (PBA) as a fluoroprobe. The NFT concentration was determined via dynamic quenching of the fluorescence of PBA. The average recovery was 96.5%-102.9%. The relative standard deviations for within-day and between-day were 3.1%-3.7% and 1.6%-3.8% respectively. The calibration curve was linear in the range from 2 micrograms.ml-1 to 100 micrograms.ml-1 with r = 0.9983. The detection limit of this method was 0.74 microgram.ml-1. The urine drug concentration-time course in rabbit after oral administration conformed to a one compartment open model with a first order absorption phase. Mean T1/2 value was 0.75 +/- 0.14 h. The selectivity was affirmed by HPTLC.

Sustained-release dosage form of nitrofurantoin. Part 2. In vivo urinary excretion in man.

The in vivo absorption of crystalline nitrofurantoin and the dosage forms of nitrofurantoin prepared with microcapsules were carried out in man by determination of urinary excretion of unchanged nitrofurantoin. The cumulative amount of drug excreted and the duration of the therapeutic urine levels were compared. The microcapsule administration showed that the peak reached during the excretion of nitrofurantoin in urine, decreased significantly when compared to the pure drug. This could be an explanation for the decrease in side-effects of nitrofurantoin such as nausea and vomiting. Experiments in male albino rats showed that the microcapsules did not produce gastric haemorrhage seen with the same doses of the pure drug.

In vitro and in vivo evaluation of seven 50 mg and 100 mg nitrofurantoin tablets.

Four 50 mg and three 100 mg marketed nitrofurantoin tablets were studied in 14 healthy male subjects. Urine was collected 1, 2, 3, 4, 6, 8, 12, and 23 h after each dose, and nitrofurantoin was assayed by HPLC. The in vitro dissolution of the tablets was determined using USP Apparatus 1 and 2, with 0.1 N hydrochloric acid and pH 7.2 buffer as the dissolution fluids. One of the 50 mg tablets was more rapidly and completely absorbed than the other six products. The incidence of side-effects for this product was as low or lower than the other products. It was determined that the use of the USP Apparatus 1, at 100 rev min-1, with sampling of the pH 7.2 fluid at 30 min, provided for the best overall relationship between the urinary excretion and in vitro dissolution.

Preparation of microcapsules from complex coacervation of Gantrez-gelatin. III. Bioavailability of nitrofurantoin microcapsules.

The bioavailability of marketed nitrofurantoin capsules was compared to capsules filled with Gantrez-gelatin nitrofurantoin microcapsules of a core:coat ratio of 1:2. The collective results obtained from the analysis of urine samples of five volunteers indicated that nitrofurantoin microcapsules provided a prolonged release compared with that of the control formulation. Analysis of variance showed statistically significant differences between the control formulation and the capsule filled with the microcapsule. Non-significant intersubject variation was noticed.

Oxidative metabolites of 5-nitrofurans.

We synthesized the 4-hydroxy derivatives of nitrofurazone, furazolidone and nitrofurantoin. Then we dosed rats orally with these antibiotics and isolated the intensely yellow, polar metabolites from their urine. A comparison of the ultraviolet and nuclear magnetic resonance spectra of these metabolites with the corresponding synthetic derivatives confirmed that the metabolites are 4-hydroxynitrofurazone, 4-hydroxyfurazolidone and 4-hydroxynitrofurantoin.

Evaluation of genotoxic activity in the blood and urine of guinea pigs treated with nifurtimox and benznidazole.

1. The mutagenicity of serum and urine from guinea pigs treated with a single oral dose (500 mg/kg) of benznidazole and nifurtimox was assayed using the Salmonella/plate incorporation test with strain TA 100 and a nitroreductase-deficient derivative, TA 100NR. 2. The urine and blood of animals treated with nifurtimox were not mutagenic for either tester strain. 3. The urine and blood of animals receiving benznidazole were mutagenic to the TA 100 but not to the TA 100NR strain. Similar results were obtained with nitrofurantoin-treated animals. Maximum mutagenicity values were obtained in serum and urine of treated animals 90 min and 24 h after administration, respectively. 4. Mutagenicity induced by benznidazole in the serum and urine of treated animals was not altered when assayed in anaerobic environments. 5. These results indicate that benznidazole and nifurtimox are not metabolized by the mammalian host into stable mutagenic derivatives detectable by the Ames test. Based on these data, we suggest that the potential cancer risk to patients treated with these drugs is small but should be further evaluated.

Correlación in vivo-in vitro en tabletas de nitrofurantoína / In vivo and in vitro correlation in nitrofurantoin tablets

Se demuestra la correlación que existe entre el ensayo de disolución dela USP XIX y el análisis de biodisponibilidad in vivo en orina

Correlación in vivo-in vitro en tabletas de nitrofurantoína / In vivo and in vitro correlation in nitrofurantoin tablets

Se demuestra la correlación que existe entre el ensayo de disolución dela USP XIX y el análisis de biodisponibilidad in vivo en orina

Urine recovery experiments with quercetin and other mutagens using the Ames test.

Recovery from urine of the mutagenic activity of 2-anthramine, cyclophosphamide, 7,12-dimethylbenz[a]anthracene, 6-chloro-9-((3-(2-chloroethylamino)-propyl)amino)-2-methoxyacridin e dihydrochloride (ICR-191), mitomycin-C, nitrofurantoin, and quercetin was studied with several of the Ames tester strains using acetone-extracted XAD-2 columns with yields ranging from 27% to 79%. Dose responses of the pure chemicals were also studied, and results showed TA 97 to be far more susceptible to quercetin mutagenesis than TA 1537. Reducing pour plate agar volume enhanced mutagenesis.

Dose- and time-dependent kinetics of the renal excretion of nitrofurantoin in the rabbit.

A pharmacokinetic study on the renal excretion of nitrofurantoin was carried out in rabbits at doses ranging from 0.5 to 15 mg/kg. With increasing dose, nonlinear kinetics were observed in the tubular secretion, which appeared to show dose and time dependence. The disposition of nitrofurantoin after intravenous injection is well described by a one-compartment model with simultaneous first-order nonrenal elimination and renal elimination, which consists of glomerular filtration, active tubular secretion conforming to the Michaelis-Menten equation, and reabsorption clearance by nonionic diffusion. Plasma and urinary excretion data after intravenous injection of nitrofurantoin were fitted to this model. When the Michaelis constant was loosely restricted at a constant value, the maximum velocity decreased with increasing dose of nitrofurantoin. However, the Michaelis constant apparently increased with increasing dose when the maximum velocity was loosely restricted at a constant value. Although the results of this fitting suggested that the former case may occur in the active tubular secretory system, the latter case could not be completely eliminated because of limited data. The implications of these results are discussed on the basis of the available published data.

Excretion studies of nitrofurantoin and nitrofurantoin with deglycyrrhizinated liquorice.

Nitrofurantoin and nitrofurantoin with liquorice were given to healthy volunteers and patients suffering from urinary tract infections. The excretion rates of the drug, colony counts and side effects were studied in patients and excretion rates in the volunteers. The excretion rates of the drug were significantly higher in patients receiving the drug with liquorice and also side effects were minimal. There was no significant difference in the excretion rates of the drug with addition of liquorice in healthy volunteers.

4-Hydroxylation of nitrofurantoin in the rat. A 3-methylcholanthrene-inducible pathway of a relatively nontoxic compound.

When nitrofurantoin was administered daily to rats, the urinary excretion of unmetabolized drug was significantly decreased after induction by 3-methylcholanthrene or beta-naphthoflavone, but was not altered after treatment with phenobarbital. In urine samples taken 36 hr after a single dose of 14C-nitrofurantoin in rats induced with 3-methylcholanthrene, the total excretion of radioactivity (30% of dose) was the same as in noninduced rats. The proportion of unchanged nitrofurantoin, however, was only 33% of the radioactivity recovered in urine from 3-methylcholanthrene-treated animals whereas in urine from control animals 76% of the activity could be attributed to the unmetabolized drug. In 6-hr urine samples one metabolite was present to a detectable extent only in urine from 3-methylcholanthrene-treated animals. The metabolite was identified as the 4-hydroxy derivative of nitrofurantoin. 4-Hydroxylation of nitrofurantoin may find use as indicator reaction for a 3-methylcholanthrene-type induction state under in vivo conditions.