Computational modeling, fabrication, and characterization of the deep eutectic solvent-based green molecular cage for selective metronidazole extraction from plasma followed by UHPLC with diode array detector determination.

Four ternary deep eutectic solvents were computationally designed and synthesized, being used as candidate functional monomers in metronidazole molecular imprinting polymer synthesis, allowing selective extraction and determination by ultra high performance liquid chromatography with diode array detection. In terms of metronidazole selective extraction, the best results were obtained by (deep eutectic solvent)2 :(ethylene glycol dimethacrylate)11 , in which deep eutectic solvent is the functional monomer constructed by combining three components in 6:6:2 ratios of choline chloride:ethylene glycol:methacrylic acid. The effects of different parameters on molecular imprinted solid-phase extraction of metronidazole were thoroughly explored through screening design and response surface methodology. The adsorption mechanism findings show that the adsorption data are primarily fitted on the Freundlich model based on higher correlation coefficient. Kinetic experiments have shown that the mechanism of adsorption fits the pseudo-second-order model. The best extraction recovery (96.5%) was obtained in 25-min elution time, desorption temperature of 40°C, and 1.0 mL ACN as eluent. Metronidazole was measured by a validated ultra high performance liquid chromatography with diode array detection method. The calibration of the method was linear in the range of 0.1-10 µg/mL with limits of detection and quantification of 0.03 and 0.1 µg/mL, respectively. The method was successfully applied for the determination of metronidazole in human plasma.

Application of the Fe3O4-chitosan nano-adsorbent for the adsorption of metronidazole from wastewater: Optimization, kinetic, thermodynamic and equilibrium studies.

The development of adsorbents with high adsorption performance is an effective method of removing metronidazole (MTZ). Therefore, Fe3O4-chitosan nano-adsorbent (CTS-MNPs) was synthesized. The SEM, TEM, FTIR, VSM and BET analyzes were applied to determine the surface morphologies, shape and size, functional groups, magnetic properties, size and volume of CTS-MNPs, respectively. R software using response surface methodology was applied to investigate the composition effect of input factors and output response. The second-order model because of insignificant lack of fit, lower P-value and also higher R2 indicated highly significant for adsorption of MTZ by CTS-MNPs. The predicted optimal conditions with considering the maximum removal efficiency (100%) were calculated for second-order model and were included (pH, 3; CTS-MNPs dosage, 2 g L-1; contact time, 90 min and MTZ concentration, 10 mg L-1). It is found that the experimental findings for the response are in good agreement with model predictions. The results declare MTZ adsorption onto CTS-MNPs involves a multilayer process (Freundlich isotherm model). Also, pseudo-second-order model indicated more appropriate for describing the MTZ adsorption onto the CTS-MNPs. The adsorption thermodynamic revealed an endothermic and spontaneous reaction for the adsorption of MTZ by CTS-MNPs.

Extraction of Metronidazole and Furazolidone from industrial effluents by double salting out assisted liquid liquid extraction technique and their analyses by HPLC-UV method.

We have developed a new analytical method for simultaneous determination of Metronidazole and Furazolidone by High Performance Liquid Chromatography (HPLC). The method is coupled to double salting-out assisted liquid-liquid extraction (SALLE) which facilitates the detection and quantification of Metronidazole and Furazolidone in different dosage forms by subsequent HPLC analysis. Extraction parameters such as solvent, pH and salt concentration are optimized and liquid liquid extraction showed efficiency up to 102% and 100% for Metronidazole and Furazolidone respectively in chloroform, at pH 3 and low salt concentration (0.5g KCl and 0.5 gNaNO3). The designed simultaneous analytical method is further validated and Metronidazole and Furazolidone showed linearity upto R20.994 and 0.9936 respectively. LOD was 2.1µg/ml, 1.5µg/ml and LOQ was 21.1µg/ml, 15.2µg/ml for metronidazole benzoate and furazolidone. Precision of the method is 1.84% (RSD) and 1.72% (RSD) for Metronidazole and Furazolidine respectively. Moreover, accuracy is measured in terms of percent recovery which is more than 100% for both analytes under optimized conditions. Finally, robustness is evaluated by changing the flow rate and detection wavelength which is also obtained within permissible limit. This indicates that the proposed method is simple, efficient and shows excellent recoveries for simultaneous determination of Metronidazole and Furazolidone in different dosage forms and Industrial effluents.

Boosted photoelectrochemical immunosensing of metronidazole in tablet using coral-like g-C3N4 nanoarchitectures.

A simple, facile and sensitive photoelectrochemical (PEC) bioassay protocol for metronidazole (MNZ) detection in common oral medicine samples has been proposed under visible-light irradiation, where novel hierarchical coral-like g-C3N4 nanoarchitectures (cg-C3N4) have been first explored as PEC sensing platform. Featured with the unique nanostructures (e.g., interlaced porous network architecture, and open boundaries), the as-formed cg-C3N4 nanoarchitectures not only efficiently inhibit the recombination of photogenerated electron-hole but also enable the immobilization of capture antibodies as well as the antibody-antigen binding efficiency fluently, thus amplifying the photocurrent response. This newly constructed PEC immunoassay displays excellent performance for MNZ determination with high sensitivity and selectivity. Under the optimal condition, this bioassay protocol exhibits a linear range of 0.01-100 µM with a detection limit of 0.005 µM at signal to noise ratio of 3. The resulting PEC immunoassay has been proved to be applicable for sensing MNZ in common oral medicine samples.

Enhancement of the adsorption capacity of the light-weight expanded clay aggregate surface for the metronidazole antibiotic by coating with MgO nanoparticles: Studies on the kinetic, isotherm, and effects of environmental parameters.

The synthesized MgO nanoparticles were used to coat the light-weight expanded clay aggregates (LECA) and as a metronidazole (MNZ) adsorbent. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier-transformed infrared (FTIR) techniques were employed to study the surface morphology and characteristics of the adsorbents. MgO/LECA clearly revealed the advantages of the nanocomposite particles, showing high specific surface area (76.12 m2/g), significant adsorption sites and functional groups. Between pH 5 and 9, the MNZ sorption was not significantly affected. Kinetic studies revealed that the MNZ adsorption closely followed the Avrami model, with no dominant process controlling the sorption rate. The study of the effects of foreign ions revealed that the addition of carbonate raised the MNZ removal efficiency of LECA by 8% and the total removal of MNZ by MgO/LECA. Furthermore, nitrate and hardness only marginally influenced the MNZ removal efficiency and their effects can be ranked in the order of carbonate>nitrate>hardness. The isotherm adsorption of MNZ was best fitted with the Langmuir model enlighten the monolayer MNZ adsorption on the homogeneous LECA and MgO/LECA surfaces. The maximum adsorption capacity under optimum conditions was enhanced from 56.31 to 84.55 mg/g for LECA and MgO/LECA, respectively. These findings demonstrated that the MgO/LECA nanocomposite showed potential as an efficient adsorbent for MNZ removal.

Enhanced ultrasound-assisted degradation of methyl orange and metronidazole by rectorite-supported nanoscale zero-valent iron.

In this study, the rectorite-supported nanoscale zero-valent iron (nZVI/R) was synthesized through a reduction method. X-ray diffraction analysis showed the existence of the nZVI in the nZVI/R composite and X-ray photoelectron spectroscopy analysis indicated that the nZVI particles were partly oxidized into iron oxide. Scanning electron microscopy analysis revealed that the nZVI particles were highly dispersed on the surface of the rectorite. The specific surface area of the nZVI/R composite is 21.43 m(2)/g, which was higher than that of rectorite (4.30 m(2)/g) and nZVI (17.97 m(2)/g). In the presence of ultrasound (US), the degradation of methyl orange and metronidazole by the nZVI/R composite was over 93% and 97% within 20 min, respectively, which is much higher than that by the rectorite and the nZVI. The degradation ratio of methyl orange and metronidazole by the nZVI/R composite under US was 1.7 and 1.8 times as high as that by the nZVI/R composite without US, respectively. The mechanism of the enhanced degradation of methyl orange and metronidazole under US irradiation was studied. These results indicate that the US/nZVI/R process has great potential application value for treatment of dye wastewater and medicine wastewater.

Analysis of metronidazole in equine plasma using liquid chromatography/tandem mass spectrometry and high-resolution accurate mass spectrometry.

RATIONALE: Treatment of racehorses with bicarbonate solutions to manage acidosis and muscle cramps prior to competition is banned in Pennsylvania (PA). Use of excess bicarbonate in horses causes diarrhea, requiring treatment with an antibiotic such as metronidazole (MTNZ). At present no method exists for detecting MTNZ in equine plasma. Thus, a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the detection, quantification and confirmation of MTNZ was developed. METHODS: The analyte was recovered from plasma by liquid-liquid extraction using methyl tert-butyl ether and separated on an ACE® C18 column with its guard column. The mobile phase comprised a mixture of 5 mM ammonium formate (pH 3.5) and acetonitrile (60:40; v/v). Mass analysis was performed on an LTQ XL linear ion trap mass spectrometer in positive electrospray ionization mode while accurate mass determination was also performed in positive electrospray ionization mode using high-resolution accurate mass spectrometry (HRAMS). RESULTS: The limit of detection (LOD), limit of confirmation (LOC) and lower limit of quantification (LLOD) were 1, 2 and 50 ng/mL, respectively. The analyte in plasma was stable at -20 and -70°C for 28 days, as well as for 24 h at 20°C in the autosampler. The percentage coefficients of variation (% CV) for the intra-day and inter-day precision for the LLOQ were 5.1:3.68 and 13.21:9.95, respectively, while the intra-day accuracy was from 98.71 to 101.57% and that of the inter-day was from 88.64 to 96.6%. The matrix effect was between 9 and 24%. The precursor → product ion transition m/z 172 → 128, a retention time of 2.92 min and the accurate mass of the [M+H](+) ion of the analyte (m/z 172.0173) were used as criteria for confirmation of the presence of MTNZ in equine plasma. CONCLUSIONS: The method is highly sensitive and selective for the detection, identification and confirmation of MTNZ in equine plasma. Thus, illegal use of MTNZ in racehorses can be routinely monitored within the US State of Pennsylvania. The method is fast, sensitive, reproducible, and reliable.

Removal of the antibiotic metronidazole by adsorption on various carbon materials from aqueous phase.

The adsorption of the antibiotic metronidazole (MNZ) on activated carbon (F400), activated carbon cloth (ACF), mesoporous activated carbon (CMK-3), and carbon nanotubes (MWCNT) was investigated in this work. The effect of the adsorbent-adsorbate interactions as well as the operating conditions (ionic strength, solution pH, temperature, chemical modification of the adsorbents by HNO3 treatment, and water matrix) on the adsorption capacity were analyzed to substantiate the adsorption mechanism. The adsorption capacity markedly varied as function of the carbon material, decreasing in the following order: F400>ACF>F400-HNO3>CMK-3>MWCNT>MWCNT-HNO3, and depended not only on their surface area and pore size distribution, but also on their chemical nature. The adsorption of MNZ was influenced by the solution pH, but was not significantly affected by the ionic strength and temperature. The adsorption of MNZ was enhanced when the MNZ solutions were prepared using wastewater. Therefore, the electrolytes present in the wastewater cooperated rather than competed with the MNZ molecules for the adsorption sites. Desorption equilibrium data of MNZ on all carbon materials demonstrated that the adsorption was reversible corroborating the weakness of the adsorbent-adsorbate interactions.

Effect of ionic crosslink on the release of metronidazole from partially carboxymethylated guar gum tablet.

Partially carboxymethylated guar gum (PCMGG) was crosslinked in situ by Ca(2+) ions during wet massing step of tablet preparation. The resulting tablets were evaluated for the effect of the extent of crosslinking on drug release and matrix swelling. Increase in the concentration of Ca(2+) ions increased the viscosity of gel layer and reduced the water penetration velocity into the matrix with subsequent decrease in swelling of the tablets and drug release. Beyond a certain concentration of Ca(2+) ions, the viscosity of the gel layer decreased and the drug release rate increased primarily due to erosion of the matrix. The mechanism of drug release appeared to be non-Fickian or anomalous transport. The release data also best fitted in zero order equation. The model drug, metronidazole, was compatible with the matrix materials as evident from instrumental analyses. Such formulation may provide flexibility in achieving the desired drug release rate from crosslinked matrix tablets.

Investigation of PAA/PVDF-NZVI hybrids for metronidazole removal: synthesis, characterization, and reactivity characteristics.

For the first time, the removal process of metronidazole (MNZ) from aqueous solutions over nano zerovalent iron (NZVI) encapsulated within poly(acrylic acid) (PAA)/poly(vinylidene fluoride) (PVDF) membranes was reported. The resultant composite (PPN) demonstrated high reactivity, excellent stability and reusability over the reaction course. Such excellent performance might be attributed to the presence of the charged carboxyl groups in PVDF membrane support, which could enhance NZVI dispersion and improve its longevity. Results showed that a lower initial concentration and higher reaction temperature facilitated the removal of MNZ by PPN, and that the acidic and neutral conditions generally exhibited more favorable effect on MNZ removal than the alkaline ones. Kinetics of the MNZ removal by PPN was found to follow a two-parameter pseudo-first-order decay model well, and the activation energy of the MNZ degradation by PPN was determined to be 30.49kJ/mol. The presence of chloride ions slightly enhanced the reactivity of PPN with MNZ, whereas sulfate ions inhibited its reactivity. In addition, MNZ degradation pathways by PPN were proposed based on the identified intermediates. This study suggests that PPN composite possessing excellent performance may be a promising functional material to pretreat antibiotic wastewaters.

Performance of microbial fuel cells on removal of metronidazole.

The microbial fuel cells (MFCs) are the focus of extensive investigation as one of the promising technologies for renewable energy generation and wastewater treatment. Two-chambered MFCs were designed to investigate the removal of metronidazole and to quantify the effect of antibiotic on the efficacy of energy generation. Using 1,000 mg glucose L(-1) containing different concentrations of metronidazole (0, 10, 30, 50 mg L(-1)) as the fuels, the corresponding power densities were 141.94, 99.23, 25.44, 16.26 mW m(-2), respectively. The adverse effect on the performance of the MFCs was reversible. The removal of metronidazole achieved 85.4% within 24 hours in MFCs, while only 35.2% in open circuit. Current generation could account for the improved removal efficiency at these tested concentration levels. The findings of this paper indicated that antibiotics such as metronidazole could be removed in MFCs, which has implications for general wastewater treatment.

Electrochemical degradation of the antibiotic metronidazole in aqueous solution by the Ti/SnO2-Sb-Ce anode.

Metronidazole (MNZ) is an antibiotic pollutant with a high occurrence in the ambient medium. In this study, the anode material Ti/SnO2-Sb-Ce prepared in the lab was employed to investigate the feasibility of the electrochemical process to treat antibiotic in wastewater. The result showed that metronidazole could be effectively removed using Ti/SnO2-Sb-Ce. The degradation efficiency of 88% was obtained under the current density 1.6 mA cm(-2), pH = 5.6 (not adjusted), electrolyte (Na2SO4) concentration of 0.2 M for electrolysis 2 h. The removal percentage was higher by 17% compared with the control when the bare Ti was applied. Meanwhile, the energy consumption on Ti/SnO2-Sb-Ce was about one-seventh of that on Ti. The characterization of the material was conducted by the thermal field emission scanning electron microscope (FE-SEM), energy-dispersive X-ray spectrometer (EDS) and cyclic voltammetry (CV). The Ti/SnO2-Sb-Ce anode displayed compact, multi-porous morphology and good redox reversibility. The influencing factors such as current density, pH, concentration of Na2SO4, initial MNZ concentration were studied to obtain main factors and optimum conditions. In addition, a preliminary study on the mechanism of the electro-oxidation was carried out. The results demonstrate that chemisorbed oxygen has a dominant role in MNZ removal.

Preparation and characterization of a molecularly imprinted monolithic column for pressure-assisted CEC separation of nitroimidazole drugs.

A polymethacrylate-based molecularly imprinted monolithic column bearing mixed functional monomers, using non-covalent imprinting approach, was designed for the rapid separation of nitroimidazole compounds. The new monolithic column has been prepared via simple in situ polymerization of 2-hydroxyethyl methacrylate, dimethylaminoethyl methacrylate and ethylene dimethacrylate, using (S)-ornidazole ((S)-ONZ) as template in a binary porogenic mixture consisting of toluene and dodecanol. The composition of the polymerization mixture was systematically altered and optimized by altering the amount of monomers as well as the composition of the porogenic solvent. The column performance was evaluated in pressure-assisted CEC mode. Separation conditions such as pH, voltage, amount of organic modifier and salt concentration were studied. The optimized monolithic column resulted in excellent separation of a group of structurally related nitroimidazole drugs within 10 min in isocratic elution condition. Column efficiencies of 99 000, 80 000, 103 000, 60 000 and 99 000 plates/m were obtained for metronidazole, secnidazole, ronidazole, tinidazole and dimetridazole, respectively. Parallel experiments were carried out using molecularly imprinted and non-imprinted capillary columns. The separation might be the result of combined effects including hydrophobic, hydrogen bonding and the imprinting cavities on the (S)-ONZ-imprinted monolithic column.

Ion mobility spectrometry as a detector for molecular imprinted polymer separation and metronidazole determination in pharmaceutical and human serum samples.

Application of ion mobility spectrometry (IMS) as the detection technique for a separation method based on molecular imprinted polymer (MIP) was investigated and evaluated for the first time. On the basis of the results obtained in this work, the MIP-IMS system can be used as a powerful technique for separation, preconcentration, and detection of the metronidazole drug in pharmaceutical and human serum samples. The method is exhaustively validated in terms of sensitivity, selectivity, recovery, reproducibility, and column capacity. The linear dynamic range of 0.05-70.00 microg/mL was obtained for the determination of metronidazole with IMS. The recovery of analyzed drug was calculated to be above 89%, and the relative standard deviation (RSD) was lower than 6% for all experiments. Various real samples were analyzed with the coupled techniques, and the results obtained revealed the efficient cleanup of the samples using MIP separation before the analysis by IMS as a detection technique.

Multivariate analysis of nystatin and metronidazole in a semi-solid matrix by means of diffuse reflectance NIR spectroscopy and PLS regression.

A multivariate method of analysis of nystatin and metronidazole in a semi-solid matrix, based on diffuse reflectance NIR measurements and partial least squares regression, is reported. The product, a vaginal cream used in the antifungal and antibacterial treatment, is usually, quantitatively analyzed through microbiological tests (nystatin) and HPLC technique (metronidazole), according to pharmacopeial procedures. However, near infrared spectroscopy has demonstrated to be a valuable tool for content determination, given the rapidity and scope of the method. In the present study, it was successfully applied in the prediction of nystatin (even in low concentrations, ca. 0.3-0.4%, w/w, which is around 100,000 IU/5g) and metronidazole contents, as demonstrated by some figures of merit, namely linearity, precision (mean and repeatability) and accuracy.

Antimicrobial resistance in Helicobacter pylori in Barbados

OBJECTIVE: Helicobacter pylori eradication is essential in patients with peptic ulcer who are infected with the organism. The rate of eradication is related to the level of antimicrobial resistance to metronidazole, clarithromycin, amoxycillin and tetracycline in H pylori in this community. DESIGN AND METHODS: Gastric biopsies from all patients undergoing upper gastrointestinal endoscopy were cultured. Isolation was done on Thayer-Martin medium under microaerophilic conditions and isolates were sub-cultured on chocolate agar. MICs were determined using the E-test. RESULTS: 64 isolates were available for testing. Metronidazole resistance (MIC > 8mg/l) was observed in 39 percent (25/64), clarithromycin resistance (MIC > 2mg/l) in 4.7 percent (3/64), amoxycillin resistance (MIC > 8mg/l) in 4.7 percent (3/64) and tetracycline resistance (MIC > 4mg/l) in 3.1 percent (2/64). CONCLUSIONS: The high level of metronidazole resistance precludes the use of this antibiotic as first line therapy for H pylori in Barbados. It is recommended that a proton pump inhibitor, amoxycillin and clarithromycin be the combination of choice for eradication of H pylori in patients in Barbados.(Au)

[Optimization of the conditions for extracting metronidazole with organic solvents]. / Optimizatsiia uslovii izvlecheniia metronidazola organicheskimi rastvoriteliami.

Optimal conditions of metronidazole extraction from aqueous solutions by different solvents using a mathematical method of experiment planning (latin square) were studied. It was stated that optimal conditions of metronidazole extraction from aqueous solutions were: extraction time (5 min.), pH medium-6, extractant-isoamyl spirit in saturation of aqueous phase with ammonium sulfate.