Isoquinolinequinone N-oxides as anticancer agents effective against drug resistant cell lines.

The isoquinolinequinone (IQQ) pharmacophore is a privileged framework in known cytotoxic natural product families, caulibugulones and mansouramycins. Exploiting both families as a chemical starting point, we report on the structured development of an IQQ N-oxide anticancer framework which exhibits growth inhibition in the nM range across melanoma, ovarian and leukaemia cancer cell lines. A new lead compound (16, R6 = benzyl, R7 = H) exhibits nM GI50 values against 31/57 human tumour cell lines screened as part of the NCI60 panel and shows activity against doxorubicin resistant tumour cell lines. An electrochemical study highlights a correlation between electropositivity of the IQQ N-oxide framework and cytotoxicity. Adduct binding to sulfur based biological nucleophiles glutathione and cysteine was observed in vitro. This new framework possesses significant anticancer potential.

Synthesis and electrochemical detection of a thiazolyl-indole natural product isolated from the nosocomial pathogen Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen, capable of surviving in a broad range of natural environments and quickly acquiring resistance. It is associated with hospital-acquired infections, particularly in patients with compromised immunity, and is the primary cause of morbidity and mortality in cystic fibrosis (CF) patients. P. aeruginosa is also of nosocomial importance on dairy farms and veterinary hospitals, where it is a key morbidity factor in bovine mastitis. P. aeruginosa uses a cell-cell communication system consisting of signalling molecules to coordinate bacterial secondary metabolites, biofilm formation, and virulence. Simple and sensitive methods for the detection of biomolecules as indicators of P. aeruginosa infection would be of great clinical importance. Here, we report the synthesis of the P. aeruginosa natural product, barakacin, which was recently isolated from the bovine ruminal strain ZIO. A simple and sensitive electrochemical method was used for barakacin detection using a boron-doped diamond (BDD) and glassy carbon (GC) electrodes, based on cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The influence of electrolyte pH on the peak potential and peak currents was also investigated. At pH 2.0, the peak current was linearly dependent on barakacin concentration (in the range used, 1-10 µM), with correlation coefficients greater than 0.98 on both electrodes. The detection limit (S/N = 3) on the BDD electrode was 100-fold lower than that obtained on the GC electrode. The optimized method using the BDD electrode was extended to bovine (cow feces) and human (sputum of a CF patient) samples. Spiked barakacin was easily detected in these matrices at a limit of 0.5 and 0.05 µM, respectively. Graphical abstract Electrochemical detection of barakacin.

One step preparation and electrochemical analysis of IQS, a cell-cell communication signal in the nosocomial pathogen Pseudomonas aeruginosa.

Pseudomonas aeruginosa uses a hierarchical cell-cell communication system consisting of a number of regulatory elements to coordinate the expression of bacterial virulence genes. Sensitive detection of quorum sensing (QS) molecules has the potential for early identification of P. aeruginosa facilitating early medical intervention. A recently isolated cell-cell communication molecule, a thiazole termed IQS, can bypass the las QS system of P. aeruginosa under times of stress, activating a subset of QS-controlled genes. This compound offers a new target for pathogen detection and has been prepared in a one step protocol. A simple electrochemical strategy was employed for its sensitive detection using boron-doped diamond and glassy carbon electrodes by cyclic voltammetry and amperometry.

CE with a boron-doped diamond electrode for trace detection of endocrine disruptors in water samples.

Off-line SPE and CE coupled with electrochemical detection have been used for the determination of bisphenol A (BPA), bisphenol F, 4-ethylphenol, and bisphenol A diglycidyl ether in bottled drinking water. The use of boron-doped diamond electrode as an electrochemical detector in amperometric mode that provides a favorable analytical performance for detecting these endocrine-disrupting compounds, such as lower noise levels, higher peak resolution with enhanced sensitivity, and improved resistance against electrode passivation. The oxidative electrochemical detection of the endocrine-disrupting compounds was accomplished by boron-doped diamond electrode poised at +1.4 V versus Ag/AgCl without electrode pretreatment. An off-line SPE procedure (Bond Elut® C18 SPE cartridge) was utilized to extract and preconcentrate the compounds prior to separation and detection. The minimum concentration detectable for all four compounds ranged from 0.01 to 0.06 µM, having S/N equal to three. After exposing the plastic bottle water container under sunlight for 7 days, the estimated concentration of BPA in the bottled drinking water was estimated to be 0.03 µM. This proposed approach has great potential for rapid and effective determination of BPA content present in water packaging of plastic bottles that have been exposed to sunlight for an extended period of time.

Analysis and electroanalysis of perchlorate in water and food samples: a critical review.

Perchlorate, ClO4-, with diverse applications, has become one of the major contaminants in surface and groundwater sources. This highly soluble and stable anion poses a considerable threat to human health given that it contaminates drinking water, vegetables, milk, and other contaminated food products. ClO4- can impair the thyroid function; thus, drinking water with high levels of this anion is a severe problem worldwide. However, due to the high solubility, stability, and mobility of ClO4-, its remediation and monitoring remain a major challenge. Considering the various analytical methods, including electrochemistry, each method has advantages and disadvantages in terms of detection sensitivity, selectivity, analysis time, and cost. Also, sample preconcentration and clean-up must be performed for the analysis of more complex matrices such as food and biological samples to ensure a low detection limit and selectivity. Both ion chromatography (IC) and capillary electrophoresis (CE) coupled with electrochemical detection, in addition to liquid chromatography (LC)-mass spectrometry (MS), are expected to play key roles due to their lower detection limit with excellent sensitivities and selectivity. Herein, we also discuss the perspective on various electrode materials for the detection of ClO4- regarding whether ClO4- can be measured at the lowest levels with the highest selectivity.

Evaluation of hydrophilic interaction chromatography versus reversed-phase chromatography for fast aqueous species distribution analysis of Nickel(II)-Histidine complex species.

Nickel (Ni) is a trace heavy metal of importance in biological and environmental systems, with well documented allergy and carcinogenic effects in humans. With Ni(II) as the dominant oxidation state, the elucidation of the coordination mechanisms and labile complex species responsible for its transportation, toxicity, allergy, and bioavailability is key to understanding its biological effects and location in living systems. Histidine (His) is an essential amino acid that contributes to protein structure and activity and in the coordination of Cu(II) and Ni(II) ions. The aqueous low molecular weight Ni(II)-Histidine complex consists primarily of two stepwise complex species Ni(II)(His)1 and Ni(II)(His)2 in the pH range of 4 to 12. Four chromatographic columns, including the superficially porous Poro-shell EC-C18, Halo RP-amide and Poro-shell bare silica-HILIC columns, alongside a Zic-cHILIC fully porous column, were evaluated for the fast separation of the individual Ni(II)-Histidine species. Of these the Zic-cHILIC exhibited high efficiency and selectivity to distinguish between the two stepwise species Ni(II)His1 and Ni(II)His2 as well as free Histidine, with a fast separation within 120 s at a flow rate of 1 ml/min. This HILIC method utilizing the Zic-cHILIC column was initially optimized for the simultaneous analysis of Ni(II)-His-species using UV detection with a mobile phase consisting of 70% ACN and sodium acetate buffer at wwpH 6. Furthermore, the aqueous metal complex species distribution analysis for the low molecular weight Ni(II)-histidine system was chromatographically determined at various metal-ligand ratios and as a function of pH. The identities of Ni(II)His1 and Ni(II)-His2 species were confirmed using HILIC electrospray ionization- mass spectrometry (HILIC-ESI-MS) at negative mode.

Porous graphitized carbon monolith as an electrode material for probing direct bioelectrochemistry and selective detection of hydrogen peroxide.

For the first time, graphitized carbon particles with a high surface area have been prepared and evaluated as a new material for probing direct electrochemistry of hemoglobin (Hb). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) imaging revealed that the carbon monolithic skeleton was constructed by a series of mesopores with irregular shapes and an average pore diameter of ~5.6 nm. With a surface area of 239.6 m(2)/g, carbon particles exhibited three major Raman peaks as commonly observed for carbon nanotubes and other carbon materials, i.e., the sp(3) and sp(2) carbon phases coexisted in the sample. A glassy carbon electrode modified with carbon monoliths and didodecyldimethylammonium bromide exhibited direct electron transfer between Hb molecules and the underlying electrode with a transfer rate constant of 6.87 s(-1). The enzyme electrode displayed a pair of quasi-reversible reduction-oxidation peaks at -0.128 and -0.180 V, reflecting the well-known feature of the heme [Fe(3+)/Fe(2+)] redox couple: a surface-controlled electrochemical process with one electron transfer. This reagentless biosensing approach was capable of detecting H(2)O(2), a simple molecule but plays an important role in analytical and biological chemistry, as low as 0.1 µM with linearity of 0.1-60 µM and a response time of <0.8 s, comparing favorably with other carbon based electrodes (5 s).

Recent advances in miniaturisation--the role of microchip electrophoresis in clinical analysis.

This review aims to highlight the current role of microchip CE (MCE) in clinical analysis to date, and also its future potential in this important area. One of the most notable advancements in separation science, which has accelerated in the last decade, has been the use of plastic and glass microchips to achieve high-speed electrophoresis separations in seconds, requiring only pico or nanolitre sample volumes. So far, in the clinical laboratory, MCE has lent itself to the resolution of very complex challenging analytes such as DNA, RNA, protein analysis, cellular components and other disease biomarkers. At present, most basic clinical laboratories rely heavily upon various kinds of enzymatic immunoassays as these methods offer speed, specificity, reliability and are well established analytical methods. However, this is not always the case, as with all analytical methods there are limitations, and sometimes enzymatic-based assays can be challenged by low-level concentration of target analytes present in samples resulting in high RSD values and results that cannot be interpreted. In some cases, this difficulty can be exasperated when complex sample matrices are presented for analysis, and interfering components result in highly exaggerated results from unwanted extra enzymatic binding. MCE may have a role in providing alternative highly sophisticated automated clinical analysis using state-of-the-art methodologies.

Histamine determination in human urine using sub-2 µm C18 column with fluorescence and mass spectrometric detection.

A fast, sensitive, and selective method for the determination of histamine in human urine samples by ultrahigh pressure liquid chromatography (LC) with fluorescence and mass spectrometry (MS) detection is investigated. A fluorescent reagent, 4-(1-pyrene) butyric acid N-hydroxysuccinimide ester was conjugated to the primary and secondary amino moieties of histamine. The structure of dipyrene-labeled histamine in human urine was determined by quadrupole time-of-flight MS with electospray ionization interface. The determination of the dipyrene derivative of histamine in urine samples was achieved within 3.9 min on an ultrahigh pressure LC Eclipse Zorbax XDB-C(18) column with 1.8 µm particle diameter. In this work, histamine separation was achieved significantly faster (3.9 min) with improved detection limit (signal-to-noise = 3) of 0.04 nM than 19.5 min with a detection limit of 0.183 nM as reported in a previous method.

Rapid and sensitive simultaneous separation and electrochemical detection of tetracaine hydrochloride and oxymetazoline hydrochloride in pharmaceutical formulations via core-shell reversed-phase liquid chromatography.

Tetracaine hydrochloride (TCH) is a nasal anesthetic and oxymetazoline hydrochloride (OZH) is a nasal decongestant. A moderate to acute overdosage of OZH and TCH can lead to mydriasis, nausea, cyanosis, tachycardia, dyspnoea, cardiovascular failure, disorientation, seizures, and even death. Liquid chromatography (LC) has been mainly utilized for the individual determination of either TCH or OZH; however, there is a need for rapid and efficient methods for simultaneous analysis in pharmaceutical formulations and aqueous samples. This study highlights the use of the fast and efficient separation capabilities of core-shell silica particles in liquid chromatography (LC) for the simultaneous determination of TCH and OZH using UV detection and the enhanced selectivity afforded by electrochemical detection at a boron-doped diamond (BDD) electrode. Rapid reversed-phase (RP) separation and detection of OZH and TCH in nasal spray and eye drops was achieved within 45 s using a poroshell 120 EC-C18 column, by adjusting the ratio of organic solvent, mobile phase pH, detection potential and mobile phase flow rate. Sensitivity was compared using ultraviolet (UV) detection at 280 nm, and ECD at + 1.3 V with detection limits of 40 and 70 nM for TCH and OZH, respectively. The developed rapid method was utilized successfully in the analysis of pharmaceutical formulations, where the estimated levels of TCH and OZH in these formulations are in agreement with the specified values outlined by the manufacturers.

Comparison between the efficiencies of sub-2 µm C18 particles packed in narrow bore columns.

The chromatographic performance of two types of core-shell particles and two fully porous particles packed in 2.1 ID × 50 mm columns was investigated. Comparisons of the performances of the EiS-150-C(18) to that of the Kinetex-1.7 µm-C(18), Acquity-BEH-1.7 µm-C(18), and Zorbax-XDB-1.8 µm-C(18) are made and discussed. The physical factors that govern the performance of these columns, such as particle size distribution and column external, total, and particle porosity of the C(18) packing materials were among the prime foci of investigation. The differences in the mass transfer behavior measured using naphtho[2,3-a]pyrene between these columns provides an indication of improved performance of the new EiS-150-C(18) column. The minimum reduced height equivalent to a theoretical plate (HETP) value for the EiS-150-C(18), h(min) = 1.95, was achieved and was comparable to that obtained from the C(18) phases of the Kinetex (h(min) = 2.53), the Acquity (h(min) = 2.26), and the Zorbax (h(min) = 2.57) columns. This study reveals the importance of the dimension of the shell thickness in controlling the performance of columns packed with shell particles in narrow bore columns.

Electrophoretic analysis of biomarkers using capillary modification with gold nanoparticles embedded in a polycation and boron doped diamond electrode.

Field-amplified sample stacking using a fused silica capillary coated with gold nanoparticles (AuNPs) embedded in poly(diallyl dimethylammonium) chloride (PDDA) has been investigated for the electrophoretic separation of indoxyl sulfate, homovanillic acid (HVA), and vanillylmandelic acid (VMA). AuNPs (27 nm) exhibit ionic and hydrophobic interactions, as well as hydrogen bonding with the PDDA network to form a stable layer on the internal wall of the capillary. This approach reverses electro-osmotic flow allowing for fast migration of the analytes while retarding other endogenous compounds including ascorbic acid, uric acid, catecholamines, and indoleamines. Notably, the two closely related biomarkers of clinical significance, HVA and VMA, displayed differential interaction with PDDA-AuNPs which enabled the separation of this pair. The detection limit of the three analytes obtained by using a boron doped diamond electrode was approximately 75 nM, which was significantly below their normal physiological levels in biological fluids. This combined separation and detection scheme was applied to the direct analysis of these analytes and other interfering chemicals including uric and ascorbic acids in urine samples without off-line sample treatment or preconcentration.

Use of cyclodextrin-modified gold nanoparticles for enantioseparations of drugs and amino acids based on pseudostationary phase-capillary electrochromatography.

The application of chemical-modified gold nanoparticles (GNPs) as chiral selector for the enantioseparation based on pseudostationary phase-CEC (PSP-CEC) is presented. GNPs modified by thiolated beta-CD were characterized by NMR and FT-IR. The nanoparticle size was determined to be of 9.5 nm (+2.5 nm) by Transmission Electron Microscopy (TEM) and UV spectra. Four pairs of dinitrophenyl-labeled amino acid enantiomers (DL-Val, Leu, Glu and Asp) and three pairs of drug enantiomers (RS-chlorpheniramine, zopiclone and carvedilol) were analyzed by using modified GNPs as the chiral selector in PSP-CEC. Good theoretical plate number (up to 2.4x10(5) per meter) and separation resolution (up to 4.7) were obtained even with low concentration of modified GNPs (0.8-1.4 mg/mL). The corresponding concentration of beta-CD in the buffer was only 0.30-0.53 mM, which was much lower than the optimum concentration of 15 mM if pure beta-CD was used as chiral selector. Our results showed that thiolated beta-CD modified GNPs have more sufficient interaction with the analytes, resulting in significant enhancement of enantioseparation. The study shed light on potential usage of chemical modified GNPs as chiral selector for enantioseparation based on PSP-CEC.

Retention and selectivity properties of carbamate pesticides on novel polar-embedded stationary phases.

This study describes the use of stationary phases with polar functionality suitable for the chemical analysis of carbamates pesticides and comparing with conventional alkyl C8 and C18 phases. The emphasis of this study was to compare the selectivity and retention of the pesticides on different stationary phases, bonded onto 1.7 microm partially porous silica particles under isocratic separation condition. Four stationary phases including: phenylaminopropyl (PAP) phase, bidentate propylurea-C18 (BPUC(18)), C8 and C18, were successfully bonded on the partially porous silica spheres as evidenced by (29)Si and (13)C solid-state NMR analysis. The phenylaminopropyl phase exhibited smaller retentivity and enhanced selectivity compared to the alkyl C8 phase; the analysis time to run separation of the six carbamate pesticides (i.e., methomyl, propoxur, carbofuran, carbaryl, isoprocarb, and promecarb) on the PAP phase was threefold faster than alkyl C8 phase. In a similar manner, the BPUC(18) phase shows similar selectivity to that of the PAP phase, but with longer retentivity; although the BPUC(18) phase is characterized with a lesser degree of retentivity for the carbamate pesticides than the conventional alkyl C18 phase. We propose that pi-pi and weak polar interactions between the carbamate pesticides and the PAP phase dominates the separation mechanism and providing a superior selectivity; faster separation time was also achieved as a result of smaller retentivity. Whereas the C8 and C18 bonded phases exhibits only hydrophobic interactions with the pesticides, leading to larger retentivity. The BPUC(18) phase is shown to interact via polar-polar interactions in addition to hydrophobic interactions with the pesticides, providing similar selectivity with the PAP phase but with larger retentivity.

Profiling of phenolic flavorings using core-shell reversed-phase liquid chromatography with electrochemical detection at a boron-doped diamond electrode.

A high-performance liquid chromatography (HPLC) method equipped with a boron-doped diamond (BDD) electrode was established for the simultaneous determination of phenol, 4-ethylphenol (4-EP), guaiacol, 4-ethylguaiacol (4-EG), 4-vinylguaiacol (4-VG), eugenol, and o-, m- and p-cresol. The separation was performed on a reversed-phase HALO C18 core-shell column (3.0 × 50 mm, 2.7 µm) with a mobile phase comprising 10 mM formate, pH 3, and 15% acetonitrile (ACN) (v/v), a flow rate of 1.5 mL/min, corresponding to a total run time of 9 min. The electrochemical detection (ECD) was set at +1.5 V vs. Pd/H2 in oxidative mode. Under optimized operating conditions, good linearity was obtained for the nine phenolics with corresponding coefficients of determination (R2) above 0.998. The limits of detection (LODs, S/N = 3) were 10 nM-1 µM, with an 80-fold increase in sensitivity for guaiacol achieved with ECD over ultraviolet (UV) detection. The sensitive and selective HPLC-ECD method was successfully applied for the identification and quantification of the nine phenolics in Islay, Irish, Scotch, and Highland whiskey samples, with significantly higher concentrations of the flavorings determined in Islay whiskey.

Selective nanomolar detection of dopamine using a boron-doped diamond electrode modified with an electropolymerized sulfobutylether-beta-cyclodextrin-doped poly(N-acetyltyramine) and polypyrrole composite film.

N-acetyltyramine was synthesized and electropolymerized together with a negatively charged sulfobutylether-beta-cyclodextrin on a boron-doped diamond (BDD) electrode followed by the electropolymerization of pyrrole to form a stable and permselective film for selective dopamine detection. The selectivity and sensitivity of the formed layer-by-layer film was governed by the sequence of deposition and the applied potential. Raman results showed a decrease in the peak intensity at 1329 cm(-1) (sp(3)), the main feature of BDD, upon each electrodeposition step. Such a decrease was correlated well with the change of the charge-transfer resistance derived from impedance data, i.e., reflecting the formation of the layer-by-layer film. The polycrystalline BDD surface became more even with lower surface roughness as revealed by scanning electron and atomic force microscopy. The modified BDD electrode exhibited rapid response to dopamine within 1.5-2 s and a low detection limit of 4-5 nM with excellent reproducibility. Electroactive interferences caused by 4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid, ascorbic acid, and uric acid were completely eliminated, whereas the signal response of epinephrine and norepinephrine was significantly suppressed by the permselective film.

Assessment of ion transfer amperometry at liquid-liquid interfaces for detection in CE.

In this research, ion transfer across the interface between two immiscible electrolyte solutions (ITIES) was used as a method of detection in a CE separation system. This method allows for the electrochemical detection of ionic analytes that cannot be easily oxidized or reduced. Method development revealed that the optimal separation conditions for three model ions (tetraethylammonium, tetrabutylammonium, and benzensulfonate) were found to be 5 mM sodium tetraborate buffer pH 9.2 with a separation voltage of 20 kV using a 40 cm, 50 microm id fused silica capillary. Constant potential amperometry and pulsed amperometric detection were applied at the ITIES in which the organic phase was gelled. A miniaturized ITIES within a pipette tip was investigated, which resulted in improved separation efficiency and LOD. To demonstrate the ability of the system to detect substances of bioanalytical interest, the beta-adrenergic receptor blockers timolol and propranolol were detected. The simplicity of the detection platform means that it may be useful for analytical situations not requiring trace or ultratrace detection capabilities.

Cyclodextrin-modified capillary electrophoresis for achiral and chiral separation of ergostane and lanostane compounds extracted from the fruiting body of Antrodia camphorata.

A CD-modified capillary electrophoretic method has been developed for achiral and chiral analysis of seven bioactive compounds isolated from the fruiting body of Antrodia camphorata. Such important target analytes exhibit similar chemical structures and are known for their diverse properties including antioxidant and anticancer effects. The analytes were separated in 25 min using a pH 9.3, 20 mM sodium borate buffer containing 20 mM methyl-beta-CD and 30 mM sulfobutylether-beta-CD. With the exception of the optical isomer pairs (antcin B or zhankuic acid A, zhankuic acid C, and antcin A), the remaining bioactive compounds including the chiral pair antcin C were baseline-separated. Analysis time was noticeably longer to baseline separate all of the above chiral pairs (approximately 38 min) by adding 5% DMF to the running buffer. The migration order was reversed compared with the HPLC elution. More hydrophobic compounds complexed favorably with methyl-beta-CD and emerged earlier in the electropherogram than their more hydrophilic counterparts which were strongly associated with sulfobutylether-beta-CD. The simple capillary electrophoretic method developed was applicable for rapid separation and characterization of several important bioactive compounds isolated from the fruiting body of A. camphorata.

Boron-doped diamond electrode: synthesis, characterization, functionalization and analytical applications.

In recent years, conductive diamond electrodes for electrochemical applications have been a major focus of research and development. The impetus behind such endeavors could be attributed to their wide potential window, low background current, chemical inertness, and mechanical durability. Several analytes can be oxidized by conducting diamond compared to other carbon-based materials before the breakdown of water in aqueous electrolytes. This is important for detecting and/or identifying species in solution since oxygen and hydrogen evolution do not interfere with the analysis. Thus, conductive diamond electrodes take electrochemical detection into new areas and extend their usefulness to analytes which are not feasible with conventional electrode materials. Different types of diamond electrodes, polycrystalline, microcrystalline, nanocrystalline and ultrananocrystalline, have been synthesized and characterized. Of particular interest is the synthesis of boron-doped diamond (BDD) films by chemical vapor deposition on various substrates. In the tetrahedral diamond lattice, each carbon atom is covalently bonded to its neighbors forming an extremely robust crystalline structure. Some carbon atoms in the lattice are substituted with boron to provide electrical conductivity. Modification strategies of doped diamond electrodes with metallic nanoparticles and/or electropolymerized films are of importance to impart novel characteristics or to improve the performance of diamond electrodes. Biofunctionalization of diamond films is also feasible to foster several useful bioanalytical applications. A plethora of opportunities for nanoscale analytical devices based on conducting diamond is anticipated in the very near future.

Selective detection of dopamine using a combined permselective film of electropolymerized (poly-tyramine and poly-pyrrole-1-propionic acid) on a boron-doped diamond electrode.

An effective and robust electrochemical approach has been developed for selective detection of dopamine in the presence of 3,4-dihydroxyphenylalanine (l-DOPA), ascorbic acid, uric acid and other dopamine metabolites. A 'layer-by-layer' film of tyramine and pyrrole-1-propionic acid (PPA) was formed by subsequent electropolymerization on a boron-doped diamond (BDD) electrode with an overall thickness of approximately 33 nm as estimated by AFM. The formation of the electropolymerized homogeneous film was also confirmed by SEM and Raman spectroscopy. The modified BDD electrode exhibited rapid response to dopamine within 6 s and a detection limit of 50 nM with excellent reproducibility. The stable electropolymerized film was capable of excluding electroactive interference from 20 microM l-DOPA, 20 microM 3,4-dihydroxyphenylacetic acid (DOPAC), and ascorbic and uric acids at normal physiological conditions (100 microM each). The modified electrode could be used for several repeated analyses of dopamine at 5 microM, without noticeable surface fouling. A plausible mechanism for permselectivity was suggested and supported by pertinent experimental data.