Spectrally tunable humic acid-based carbon dots: a simple platform for metronidazole and ornidazole sensing in multiple real samples.

Humic acid-based carbon dots (HACDs) have excellent properties and are widely used in environmental detection, bioimaging, and optoelectronic materials. Herein, we investigated the structure-activity relationship between the morphology and optical properties of HACDs, and reported on a novel strategy for metronidazole (MNZ) and ornidazole (ONZ) sensing in multiple real samples. It was found that the average particle size decreased from 3.28 to 2.44 nm, optimal emission wavelength was blue-shifted from 500 to 440 nm, and the quantum yield (QY) improved from 5 to 23% with the temperature increasing from 110 to 400 °C. Under the oxidation of hydrogen peroxide (H2O2) and potassium permanganate (KMnO4), the UV-vis spectra of HACD aqueous solution showed time-dependent behavior, and the fluorescence emission of HACDs achieved spectrally tunable multi-color luminescence in the temporal dimension. The surface of HACDs contained a large number of hydroxyl (-OH) and carboxyl (-COOH) fluorophores, resulting in excellent pH sensing. Meanwhile, the synthesized HACDs revealed sensitive response to MNZ and ONZ with the limit of detection (LOD) of 60 nM and 50 nM in aqueous solutions, which had also been successfully applied in various actual samples such as lake water, honey, eggs, and milk with satisfactory results because of the inner filter effect (IFE). Our research is advantageous to enhance the potential applications of HACDs in advanced analytical systems.

Development and characterization of rapid dissolving ornidazole loaded PVP electrospun fibers.

Gingivitis is a common and mild form of periodontal disease and can be described as a limited inflammation of the gingiva. This study aims to develop and characterize rapid releasing mucoadhesive fibers containing ornidazole with electrospinning process for the treatment of gingivitis. Polyvinylpyrrolidone (PVP) was chosen as a polymer and used at different concentrations of 10%, 12.5%, and 15%. Scanning electron microscopy images showed that fiber diameters increased with increasing polymer concentrations. Tensile strength and elongation at break values of fibers increased with increasing PVP amount, whereas the loading of ornidazole into the fibers decreased these parameters. The contact angle values of all fibers were found to be 0° due to the hydrophilic nature of PVP. Ornidazole was released within 5 min and diffused from all of the fibers faster than that of gel and solution formulations. Electrospun ornidazole fibers were found efficient against Porphyromonas gingivalis in antimicrobial activity studies. The results demonstrated that ornidazole loaded fibers could be a potential drug delivery system for the treatment of gingivitis.

Preparation, in Vitro and in Vivo Evaluations of Compound Calculus Bovis Sativus and Ornidazole Film.

The aim of this study was to develop and to investigate a film of compound Calculus Bovis Sativus (CBS) and ornidazole film. A uniform mucoadhesive film was herein successfully obtained by a film-forming solusion containing insoluable drug. This film, as a valid adjunct for the treatment of oral mucosal ulcer, consisted of two main drugs (CBS, ornidazole) and three polymers (hydroxypropyl methyl cellulose, chitosan, poly(vinyl alcohol) (PVA)). The film was prepared with the film-forming suspension, using casting-solvent evaporation technique. The drug content, release behavior, swelling index and mucoadhesive properties of the film were detected. Then the effects of the prepared film on a glacial acetic acid-induced oral mucosal ulceration model of rabbits were evaluated. Moreover, the in vivo release of bilirubin and ornidazole in saliva were also detected in the oral mucosae of healthy volunteers. The films showed favorable in vitro drug release behaviors and swelling properties. Mucosal wounds in the animals were significantly relieved. With the films well tolerated, the salivary concentrations of ornidazole were maintained above the minimum inhibitory concentration against CBS for about 2 h. The compound CBS and ornidazole film functioned better than the film only containing CBS and ornidazole did. Therefore, it is a potentially efficient drug delivery system for the treatment of oral ulcers.

In vitro simulation of in vivo pharmacokinetic model with intravenous administration via flow rate modulation.

The aim of this paper was to propose a method of flow rate modulation for simulation of in vivo pharmacokinetic (PK) model with intravenous injection based on a basic in vitro PK model. According to the rule of same relative change rate of concentration per unit time in vivo and in vitro, the equations for flow rate modulation were derived using equation method. Four examples from literature were given to show the application of flow rate modulation in the simulation of PK model of antimicrobial agents in vitro. Then an experiment was performed to confirm the feasibility of flow rate modulation method using levo-ornidazole as an example. The accuracy and precision of PK simulations were evaluated using average relative deviation (ARD), mean error and root mean squared error. In vitro model with constant flow rate could mimic one-compartment model, while the in vitro model with decreasing flow rate could simulate the linear mammillary model with multiple compartments. Zero-order model could be simulated using the in vitro model with elevating flow rate. In vitro PK model with gradually decreasing flow rate reproduced the two-compartment kinetics of levo-ornidazole quite well. The ARD was 0.925 % between in vitro PK parameters and in vivo values. Results suggest that various types of PK model could be simulated using flow rate modulation method without modifying the structure. The method provides uniform settings for the simulation of linear mammillary model and zero-order model based on in vitro one-compartment model, and brings convenience to the pharmacodynamic study.

Inner reorganization limiting electron transfer controlled hydrogen bonding: intra- vs. intermolecular effects.

In this work, experimental evidence of the influence of the electron transfer kinetics during electron transfer controlled hydrogen bonding between anion radicals of metronidazole and ornidazole, derivatives of 5-nitro-imidazole, and 1,3-diethylurea as the hydrogen bond donor, is presented. Analysis of the variations of voltammetric EpIcvs. log KB[DH], where KB is the binding constant, allowed us to determine the values of the binding constant and also the electron transfer rate k, confirmed by experiments obtained at different scan rates. Electronic structure calculations at the BHandHLYP/6-311++G(2d,2p) level for metronidazole, including the solvent effect by the Cramer/Truhlar model, suggested that the minimum energy conformer is stabilized by intramolecular hydrogen bonding. In this structure, the inner reorganization energy, λi,j, contributes significantly (0.5 eV) to the total reorganization energy of electron transfer, thus leading to a diminishment of the experimental k.

Investigation of chiral inversion and pharmacokinetics of laevo-ornidazole by high-performance liquid chromatography.

WHAT IS KNOWN AND OBJECTIVE: Laevo-ornidazole is an enantiomer of ornidazole, a 5-nitroimidazole antimicrobial agent. It is not known whether chiral inversion of laevo-ornidazole occurs in humans. The objective of this study was to investigate the possible chiral inversion and pharmacokinetics of the drug in vivo. METHODS: We developed a stereo-specific high-performance liquid chromatographic method for investigating chiral inversion of the drug and a standard high-performance liquid chromatography (HPLC) for the routine assay of the drug in pharmacokinetic studies. We report on the pharmacokinetics of the drug following single dose and multiple doses and investigate the effect of food in healthy volunteers. RESULTS AND DISCUSSION: There was no chiral inversion of laevo-ornidazole in vivo. In the pharmacokinetic study of the drug in healthy Chinese volunteers, food intake affected the absorption rate of laevo-ornidazole but not the extent. WHAT IS NEW AND CONCLUSION: We present the first reported method for the chiral separation of ornidazole in human plasma. We demonstrate the absence of chiral inversion of laevo-ornidazole in vivo. Given the absence on in vivo chiral inversion, we also report and validate a simplified non-chiral method for the determination of laevo-ornidazole. We show that although food can affect the absorption rate of laevo-ornidazole, the extent was unaffected.

Formulation and development of oral dry suspension using taste masked Ornidazole particles prepared using Kollicoat(®) Smartseal 30 D.

The purpose of this work was to taste mask highly bitter active, Ornidazole by means of particle coating. The aim of the work was further extended into formulating these coated particles into an acceptable oral dosage form such as dry suspension. Ornidazole drug particles were coated using Kollicoat(®) Smartseal 30 D as a taste masking polymer. Kollicoat(®) Smartseal 30 D is a methyl methacrylate - diethylaminoethyl methacrylate copolymer (6:4). Successful taste masking was achieved for Ornidazole with both top spray and bottom spray techniques using fluid bed processor. Effective taste masking was achieved at a weight gain of 50% w/w and 40% w/w for bottom and top spray techniques respectively without having a significant effect on the release pattern. A taste masked dry suspension was prepared with around 80% w/w coated Ornidazole particles and pH was maintained around 7-8. The suspension prepared with these coated Ornidazole particles, which were maintained in the alkaline pH was found to be stable for 7 days without affecting the taste. The bitter taste intensity was evaluated using volunteers by comparison of test samples with standard solutions containing Ornidazole at various concentrations. Thus, Kollicoat(®) Smartseal 30 D was found to be an effective polymer for taste masking of a bitter active like Ornidazole. The formulation development of taste masked dry suspensions was only possible due to unique properties possessed by Kollicoat(®) Smartseal 30 D.

Fenton-Like Oxidation of Antibiotic Ornidazole Using Biochar-Supported Nanoscale Zero-Valent Iron as Heterogeneous Hydrogen Peroxide Activator.

Biochar (BC)-supported nanoscale zero-valent iron (nZVI-BC) was investigated as a heterogeneous Fenton-like activator to degrade the antibiotic ornidazole (ONZ). The characterization of nZVI-BC indicated that BC could enhance the adsorption of ONZ and reduce the aggregation of nZVI. Thus, nZVI-BC had a higher removal efficiency (80.1%) than nZVI and BC. The effects of parameters such as the nZVI/BC mass ratio, pH, H2O2 concentration, nZVI-BC dose, and temperature were systematically investigated, and the removal of ONZ followed a pseudo-second-order kinetic model. Finally, possible pathways of ONZ in the oxidation process were proposed. The removal mechanism included the adsorption of ONZ onto the surface of nZVI-BC, the generation of •OH by the reaction of nZVI with H2O2, and the oxidation of ONZ. Recycling experiments indicated that the nZVI-BC/H2O2 system is a promising alternative for the treatment of wastewater containing ONZ.

Study of polymorphic transformation of ornidazole drug by differential scanning calorimetry and other complementary techniques.

Differential scanning calorimetric (DSC) curves recorded for ornidazole drug during heating and cooling showed that the drug which melted around 86.1 degrees C undercooled to well below ambient room temperature of 27 degrees C during the cooling cycle. The undercooled melt kept in the freezer at 0 degree C for 10 days duration also remained in the viscous liquid form. This liquid on taking out from the freezer after ten days and ageing at ambient room temperature of 27 degrees C for 12 h transformed into white powder. The DSC pattern recorded for this white powder consisted of two prominent endothermic peaks beginning at 73.2 and 85.9 degrees C, respectively, suggesting that the powder consisted of a mixture of more than one phase. The X-ray diffraction (XRD) pattern recorded for this powder showed it to be a mixture of semi-crystalline phase and the original compound. The semi-crystalline phase melted at 73.2 degrees C prior to the melting of original compound at 85.9 degrees C. This phase on further ageing for 7 days transforms almost completely to its original form. DSC observations were corroborated by XRD and scanning electron microscopy (SEM) techniques.

Analytical investigation of the influence of ornidazole on the native protein fluorescence.

A novel spectrofluorimetric method for the determination of ornidazole (ORN) in pure form and dosage forms was developed based on the influence of ORN on the native fluorescence of bovine serum albumin (BSA) in a stimulated physiological environment. The obtained data reveal that the presence of ORN has a strong quenching effect on the fluorescence of BSA through both a dynamic and a static process. The parameters of the binding of ORN to BSA were calculated at different temperatures. Thermodynamic parameters values suggest a role of electrostatic and hydrophobic forces in the binding of ORN to BSA. The investigated method for the determination of ORN is accurate, precise and sensitive with a detection limit of 0.106 µg/mL and a quantification limit of 0.353 µg/mL. The quenching method was applied successfully in the determination of ORN in pure form and dosage forms.

Decomposition of antibiotic ornidazole by gamma irradiation in aqueous solution: kinetics and its removal mechanism.

An efficient gamma radiolytic decomposition of one of the extensively used pharmaceutical ornidazole (ORZ) was explored under different experimental conditions by varying initial concentrations, solution pHs, and doses and concentrations of inorganic ([Formula: see text]) and organic (t-BuOH) additives. The results showed that low ORZ concentrations could be efficiently decomposed using gamma irradiation. The decomposition was followed by pseudo first-order reaction kinetics with rate constant values of 2.34, 1.48, 1.11, and 0.80 kGy-1 for the following initial concentrations: 25, 50, 75, and 100 mg L-1 with their corresponding (G(-ORZ)) values of 1.004, 1.683, 2.237, and 2.273, respectively. Decomposition rate of ORZ was remarkably improved under acidic condition when compared to neutral or alkaline medium. It was also observed that the decomposition was primarily caused by the reaction of ORZ with radiolytically generated reactive HO• radicals. The addition of H2O2 had a synergistic effect on the decomposition and mineralization extent of ORZ. However, the removal of total organic carbon (TOC) was not as effective as the decomposition of ORZ. Finally, the quantum chemical calculations were employed to optimize the geometry structure of ORZ and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was used to identify the decomposition intermediates. On the basis of Gaussian calculations and analysis of LC-QTOF-MS, it can be inferred that ORZ radiolytic decomposition was mainly attributed to oxidative HO• radicals and the direct cleavage of ORZ molecules. Possible pathways for ORZ decomposition using gamma irradiation in aqueous medium were proposed.

Determination of the sulfate and glucuronide conjugates of levornidazole in human plasma and urine, and levornidazole and its five metabolites in human feces by high performance liquid chromatography-tandem mass spectrometry.

Levornidazole is a novel third-generation nitroimidazoles antibiotic which metabolism and disposition in human are not well known. We have previously developed two methods to quantify levornidazole and its phase I metabolites, Ml (Hydroxylation metabolite), M2 (N-dealkylation metabolite) and M4 (Oxidative dechlorination metabolite), in human plasma and urine. In this study, we developed three novel liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods and analyzed its phase II metabolites, sulfate conjugate (M6) and glucuronide conjugate (M16), in human plasma and urine, and the parent drug and above-mentioned five metabolites in human feces samples. Analytes and internal standard (IS) in human plasma were extracted by a solid-phase extraction procedure and separated on an ACQUITY UPLC CSH C18 column in gradient elution using acetonitrile and 0.1% formic acid aqueous solution as the mobile phase. The pretreatment procedures for urine and feces homogenate samples involved a protein precipitation followed by liquid-liquid extraction, and chromatographic separations were performed on the Atlantis T3 columns of different lengths and particle sizes (2.1 × 50 mm, 3 µm and 2.1 × 150 mm, 5 µm), respectively. The mobile phases consisted of formic acid and acetonitrile-methanol solution (v/v, 50:50) in gradient elution. The MS/MS analysis was conducted on TSQ Quantum triple quadrupole mass spectrometer using electrospray ionization with selected reaction monitoring (SRM) in the positive ion mode. The calibration curves for all analytes were linear and the validation ranges were as follows: 0.005-0.500 µg/mL for M6 and 0.005-2.500 µg/mL for M16 in plasma; 0.010-10.000 µg/mL for M6 and M16 in urine; 0.005-1.000 µg/mL for levornidazole, M2, M4 and M16, and 0.010-2.000 µg/mL for M1 and M6 in human feces homogenate. Across these matrices, mean intra- and inter- batch accuracy values were in the ranges of 80.0%-120.0%, and intra- and inter-batch precision values did not exceed 20%. It was fully validated including selectivity, linearity, matrix effect, extraction recovery, stability, dilution integrity, carryover and incurred sample analysis (ISR). These newly developed methods were successfully applied in pharmacokinetics, metabolism and disposition study of levornidazole in 12 healthy Chinese subjects.

Enzyme sensitive smart inulin-dehydropeptide conjugate self-assembles into nanostructures useful for targeted delivery of ornidazole.

Molecular self-assembly of biodegradable amphiphilic polymers allows rational design of biocompatible nanomaterials for drug delivery. Use of substituted polysaccharides for such applications offers the ease of design and synthesis, and provides higher biofunctionality and biocompatibility to nanomaterials. The present work focuses on the synthesis, characterization and potential biomedical applications of self-assembled polysaccharide-based materials. We demonstrated that the synthesized amphiphilic inulin self-assembled in aqueous medium into nanostructures with average size in the range of 146-486nm and encapsulated hydrophobic therapeutic molecule, ornidazole. Hydrophophic dehydropeptide was conjugated with inulin via a biocompatible ester linkage. Dehydrophenylalanine, an unusual amino acid, was incorporated in the peptide to make it stable at a broader range of pH as well as against proteases. The resulting core-shell type of nanostructures could encapsulate ornidazole in the hydrophobic core and released it in a controlled fashion. By taking the advantage of inulin, which gets degraded in the colon by colonic bacteria, the effect of enzyme, inulinase, present in the microflora of the large intestine, on inulin-peptide degradation followed by drug release has been studied. Altogether, small peptide conjugated to inulin offers novel scaffold for the future design of nanostructures with potential applications in the field of targeted drug delivery.

Design, optimization and characterizations of chitosan fortified calcium alginate microspheres for the controlled delivery of dual drugs.

Periodontal disease is chronic, highly prevalent infectious disease that requires prolonged and controlled delivery of antimicrobial agents into pockets. To achieve this objective, dual antimicrobials encapsulated chitosan fortified calcium alginate (CS-Ca-SA) microspheres were formulated by application of Plackett-Burman factorial design. The microspheres were optimized for particle size (PS), entrapment efficiency (EE) and drug release. The optimized microspheres presented average PS of 74-461 µm and EE of 62.45-86.20% with controlled drug delivery for 120 hours. FTIR disclosed successful complexation between SA and CS. DSC and XRD studies showed changes in the crystallinity of drugs in microspheres. Shape factor and SEM demonstrated spherical to pear-shaped microspheres. Release exponent >0.43 and high diffusion coefficients revealed non-Fickian-based diffusion-limited drug release. CS-Ca-SA microspheres exhibited surface pH of 6.5 ± 0.5, moderate swelling, less erosion and improved mucoadhesion over Ca-SA microspheres. Also, significant antimicrobial activity against Escherichia coli and Staphylococcus aureus and cytocompatibility with L929 cell lines were observed. Further, microspheres exhibited long-term stability on refrigeration. The outcomes of study supported the potential of dual polymer and dual drug-based biodegradable, stable, non-toxic, mucoadhesive, controlled and prolonged drug release microspheres as more patient compliant by administration into periodontal pockets for the management of periodontal disease.

Multiparticulate based thermosensitive intra-pocket forming implants for better treatment of bacterial infections in periodontitis.

Considering alarming projections in the prevalence of periodontitis, following study was undertaken to develop chitosan-vanillin crosslinked microspheres loaded in-situ gel (MLIG) implants containing ornidazole and doxycycline hyclate for the treatment of pocket infections. Firstly, microspheres were formulated and optimized using response surface methodology for particle size <50 µm, entrapment efficiency >80%, in-vitro drug release (T80%) >7 days and acceptable mucoadhesion. Further, MLIG were optimized for gelation temperature of 34-37 °C and viscosity <1000 cps respectively. FTIR, DSC and XRD graphs disclosed compatibility and alterations in crystallinity of drugs. In-vitro dissolution study demonstrated non-Fickian type of drug release mechanism for twelve days. Stability studies ascertained MLIG implants were sterilizable and stable for about 11.29 months on refrigeration. The formulations exhibited significant (p < 0.001) antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis, and were found biocompatible and biodegradable during preclinical studies. Ligature-induced periodontal rat model, corroborated significant growth (p < 0.05) of gingival tissue after two weeks. Clinical trials revealed, intra-pocket administration of MLIG along with SRP provided significant reduction in clinical parameters as compared to SRP alone. Conclusively, antimicrobials incorporated thermosensitive, biodegradable, mucoadhesive and syringeable MLIG implants appeared as better option for the treatment of periodontitis.

W/O/W multiple emulsions containing nitroimidazole derivates for vaginal delivery.

The aim of our study was to formulate a stable multiple emulsions containing two nitroimidazole derivates, metronidazole (MT) and ornidazole (OR), for vaginal therapy. MT and OR were located internal and external phases of multiple emulsion, respectively, and the in vitro release studies were realized in phosphate (pH 7) and lactate buffer (pH 4.5) solutions to investigate better the effect of pH and location of active substance on the release. The imaging studies were realized in rabbits following labeling MT and OR with Technethium-99m ((99m)Tc) to evaluate the in vivo absorption characteristics. The percentage of MT and OR released from the multiple emulsions in alkaline media were 3.2- and 2.8-fold greater than that observed in acidic media, respectively, when they were introduced in the internal phase of the multiple emulsions. The absorption rate of MT from vaginal epithelium was faster than OR. We observed that especially in alkaline medium a high release was found that was convenient for the vaginal infections seen in the alkaline pH. We concluded that W/O/W multiple emulsions were locally effective in vagina and they could be introduced as a new drug carrier system for vaginal delivery.

Multi-Stimuli Responsive Self-Assembled Nanostructures Useful for Colon Drug Delivery.

Self-assembled nanoformulations have been finding various applications in biomedical sciences. Here, we have designed and synthesized a small molecule-based amphiphilic conjugate of azobenzene, Azo-PEG-OMe, which self-assembles into nanostructures in an aqueous environment. The formation of nanostructures was evidenced by light scattering and electron microscopic analyses, which revealed the size of the so formed nanostructures ~199 and ~42 nm, respectively. Responsiveness of these nanostructures to various stimuli was demonstrated by enzyme and UV-Vis light exposure, pH and chemical reductant, sodium dithionite. Morphological alterations in the nanostructures on exposure to these stimuli were recorded and subsequently, these nanostructures were demonstrated as efficient carrier of drugs by entrapping an antiprotozoan drug, ornidazole, with ~82% entrapment efficiency. Under influence of different stimuli (light, pH, and enzyme), the drug release behavior displayed good response to each stimulus implying that the projected nanostructures could be used as efficient drug delivery system. Response to azoreductase enzyme further established that the formulation can be used for site specific drug delivery particularly useful for colonic drug delivery.

Self-assembled dehydropeptide nano carriers for delivery of ornidazole and curcumin.

In the recent studies, it has been demonstrated that incorporation of unnatural amino acid, α,ß-dehydrophenylalanine, in small peptides results in stable self-assembled nanostructures with different sizes and shapes. Here, we have replaced the natural amino acid, phenylalanine, from our earlier reported work on self-assembled peptide, Boc-Pro-Phe-Gly-OMe, with a constrained dehydro amino acid, α,ß-dehydrophenylalanine, to study its influence on self-assembled nanostructures. Dehydrotripeptide, Boc-Pro-ΔPhe-Gly-OMe, self-assembled into nanostructures in aqueous solutions and formed hydrophobic matrix with improved encapsulation efficiency of hydrophobic molecules. The hydrodynamic size of peptide nanostructures from DLS study was found to be ∼257nm. The morphology and size of the loaded nanoparticles were also determined by TEM. To improve aqueous dispersibility the projected nanostructures for efficient use in drug delivery, self-assembled dehydropeptide nano carriers were further stabilized with Vitamin-E-TPGS. The final complex drug nanoparticles provided controlled drug release. These findings demonstrated that incorporation of constrained dehydro amino acids in peptides have the potential to construct stable nanostructures for development of nano materials with controlled drug release.

Experimental and theoretical study of ornidazole.

The Fourier transform infrared (FT-IR) and the Fourier transform Raman (FT-Raman) spectra of the title molecule in solid phase were recorded in the region 4000-400 cm(-1) and 4000-100 cm(-1) respectively. The geometrical parameters and energies were investigated with the help of Density Functional Theory (DFT) employing B3LYP method and 6-31G (d, p) basis set. The analysis was supported by electrostatic potential maps and calculation of HOMO-LUMO. UV, FT-IR and FT-Raman spectra of ornidazole were calculated and compared with experimental results. Thermodynamic properties like entropy, heat capacity, have been calculated for the molecule. The predicted first hyperpolarizability also shows that the molecule might have a reasonably good non-linear optical (NLO) behavior. The intramolecular contacts have been interpreted using natural bond orbital (NBO) and natural localized molecular orbital (NLMO) analysis.

Optochemical sensor for an ornidazole assay using 1-amino-4-allyloxyanthraquinone as a fluorescent indicator.

To improve the stability of optochemical sensors (optodes), the fluorescence indicator 1-amino-4-allyloxyanthraquinone (AAA), which was synthesized by reacting allyl bromide with 1-amino-4-hydroxyanthraquinone, was covalently immobilized on surface-modified glass slides. The resulting sensor was used to determine the content of ornidazole based on fluorescence quenching. It showed a linear response toward ornidazole in the concentration range of 9.0 x 10(-6) to 1.0 x 10(-3) mol L(-1) with a detection limit of 8 x 10(-6) mol L(-1) at pH 7.5. This AAA-immobilized sensor has a rapid response, high stability and good selectivity to ornidazole.