Jean-Michel Kauffmann

Research in Drug Development (RD3)

Pharmacognosy Bioanalysis and Drug Discovery

Professor Jean-Michel Kauffmann was born in Arlon, Belgium, in 1954. He became a pharmacist from the University Libre de Bruxelles (ULB) in 1977 and earned a Ph.D. degree in pharmaceutical sciences in 1983 from the same University. He became Full Professor and Head of the laboratory of instrumental analysis and bioelectrochemistry at the Institute of Pharmacy of the University Libre de Bruxelles in 1992. He is currently (2019) head of the department of research in drug development at the Faculty of Pharmacy (ULB).

Research activities

His research interests include analytical chemistry in general and more specifically electroanalysis of compounds of pharmaceutical interest, modified electrodes and biosensors and electrochemical detectors development for flow injection and HPLC analyses.

He has published 175 original papers and 24 chapters related to electroanalysis and biosensors and edited one book in the field of electroanalysis in the biomedical and pharmaceutical sciences (Spinger-2015) and given more than 300 lectures at national and international meetings.

He is the Editor-in-Chief of Talanta since 1995 and a member of the Advisory Boards of Analytical Letters, Electroanalysis, Talanta Current Separations, Chimica Acta Turcica, J.Pharm.Belgique, FABAD, (J. Pharm. Sciences of Ankara), The Open Anal.Chem. Journal, Anal.Pharm.Française, Arabian J. Chem., Farmacia (Romanian review).

Top ten recent articles

Articles dans des revues avec comité de lecture

2022

Editorial: Trends in analytical methods for customs laboratories

Benchtop NIR standardization on handheld spectrometers to identify paracetamol tablets

Near-infrared spectroscopy (NIRS) allows innovative applications in terms of quality control, for example, in raw materials verification, in process analytical technology (PAT), and in discrimination between genuine and falsified medicines. The development of small and cheap handheld devices is expanding in the field, while trying to keep similar performances as benchtop instruments have. Considering traceability and quality control of drug compounds, this work is intended to identify 13 different paracetamol tablets on the Belgian market by using NIRS. The performances of a Fourier-transform near-infrared spectroscopy (FT-NIR) benchtop and two handheld NIR spectrometers were investigated comparatively. All spectra were collected through the blister in the reflectance diffuse mode. NIR spectral fingerprints were pretreated and analyzed using principal component analysis (PCA) and classified with soft independent modeling of class analogy (SIMCA). The performances of the spectrometers were evaluated after standardization of the reference benchtop database to the handheld spectrometers. The instrumental response of the benchtop spectrometer was standardized towards the handheld device using the piecewise direct standardization (PDS) algorithm. These investigations permitted the advantages and limitations of NIR data standardization on predictive models to be pointed out. The SIMCA models based on the spectral data of the benchtop (B), handheld 1 (H1), and handheld 2 (H2) instruments had an accuracy of 99.2%, 97.7%, and 96.2%, respectively. The same accuracy was obtained with the models of the transferred benchtop spectra for the H1 and H2 devices. However, adding handheld spectra to the transferred benchtop spectra resulted in models with improved accuracy: from 97.7% to 98.5% for the H1 instrument and from 96.2% to 97.7% for the H2 instrument. The proposed strategy highlights the potential of using a reference database collected by NIRS for pharmaceutical analyses by handheld NIR spectrometers in terms of traceability.

2021

Determination of the quality of metronidazole formulations by near-infrared spectrophotometric analysis

In the quality control of medicines and the fight against the phenomenon of poor quality medicines, there is an urgent need for rapid and broad spectrum methods for screening these types of medicines. In the present work, we have used near infrared spectroscopy combined with multivariate data analysis to develop chemometric models for the classification and quantification of metronidazole in Burkina Faso pharmaceutical formulations. For this purpose, drug samples were collected in drugstores located in different Burkina Faso border zones. Four product classes were defined based on the national nomenclature: 3 classes for the generic drugs (C1, C3, and C4) and one class for the reference (C2) drugs. The exploratory analysis using PCA identified two clusters of drugs within class C1. Discrimination was confirmed by the developed and optimised DD-SIMCA model, with only one target class. The quality control of the samples from product class C1 was proven to be very satisfactory with specificities and sensitivities of 100%. The quantification models developed with the PLS-R method were successfully applied for the determination of the active ingredient content in the samples, with acceptable relative bias between 0.15 and 12.7 % with respect to the dose determined by the HPLC method. The RMSEC was estimated at 13.57 (R2, 0.9937), the RMSECV at 18.07 (R2, 0.9888) and the RMSEP at 13.69 (R2, 0.9941).The models developed and the results obtained are promising for routine quality control of similar formulations of metronidazole.

2020

CBD oils on the Belgian market: A validated MRM GC-MS/MS method for routine quality control using QuEChERS sample clean up

Discrimination of legal and illegal Cannabis spp . according to European legislation using near infrared spectroscopy and chemometrics

Aerial parts containing cannabidiol can be purchased in a legal way but cannabis used as recreational drug is illegal in most European countries. Δ9-tetrahydrocannabinol is one of the main cannabinoids responsible for the psychotropic effect. European Union countries and Switzerland authorize a concentration of THC of 0.2 % and 1.0 % w/w, respectively, for smoking products and industrial hemp. Public health inspectors and law enforcement officers need to check the legality of samples. Therefore there is a need for innovative approaches, allowing quality control of these products in an easy way and preferably on site. In many countries, cultivation of industrial hemp is permitted if the THC content does not exceed 0.2 % w/w. A portable equipment could be a useful measuring tool for farmers to check for the THC content at regular time. In this work, 189 samples were analysed with a benchtop and a handheld NIR device in order to create two classification methods according to European and Swiss laws. All samples were also analysed by GC-FID to determine their THC concentration. Supervised analysis was applied in order to establish the best model. For the first classification, the accuracy was 91% for the test set with the benchtop data and 93 % for the test set with the handheld data. For the second classification, the accuracies were respectively 91 % and 95 %. The obtained models, hyphenating spectroscopic techniques and chemometrics, enable to discriminate legal and illegal cannabis samples according to European and Swiss laws.

2019

Isoniazid Bactericidal Activity Involves Electron Transport Chain Perturbation.

Accumulating evidence suggests that the bactericidal activity of some antibiotics may not be directly initiated by target inhibition. The activity of isoniazid (INH), a key first-line bactericidal antituberculosis drug currently known to inhibit mycolic acid synthesis, becomes extremely poor under stress conditions, such as hypoxia and starvation. This suggests that the target inhibition may not fully explain the bactericidal activity of the drug. Here, we report that INH rapidly increased Mycobacterium bovis BCG cellular ATP levels and enhanced oxygen consumption. The INH-triggered ATP increase and bactericidal activity were strongly compromised by Q203 and bedaquiline, which inhibit mycobacterial cytochrome bc1 and FoF1 ATP synthase, respectively. Moreover, the antioxidant N-acetylcysteine (NAC) but not 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) abrogated the INH-triggered ATP increase and killing. These results reveal a link between the energetic (ATP) perturbation and INH's killing. Furthermore, the INH-induced energetic perturbation and killing were also abrogated by chemical inhibition of NADH dehydrogenases (NDHs) and succinate dehydrogenases (SDHs), linking INH's bactericidal activity further to the electron transport chain (ETC) perturbation. This notion was also supported by the observation that INH dissipated mycobacterial membrane potential. Importantly, inhibition of cytochrome bd oxidase significantly reduced cell recovery during INH challenge in a culture settling model, suggesting that the respiratory reprogramming to the cytochrome bd oxidase contributes to the escape of INH killing. This study implicates mycobacterial ETC perturbation through NDHs, SDHs, cytochrome bc1, and FoF1 ATP synthase in INH's bactericidal activity and pinpoints the participation of the cytochrome bd oxidase in protection against this drug under stress conditions.

Isoniazid bactericidal activity involves electron transport chain perturbation

2018

Determination of three main chlorogenic acids in water extracts of coffee leaves by liquid chromatography coupled to an electrochemical detector

Coffee is a beverage widely consumed in the world. The coffee species most commercialized worldwide are Arabica (Coffea arabica) and Robusta (Coffea canephora). Roasted coffee beans are the most used, but coffee leaves are also consumed as infusion in several countries for traditional medicinal purposes. They contain several interesting phenolic antioxidant compounds mainly belonging to chlorogenic acids (CGAs). In the present work, a liquid chromatography-electrochemical detection (LC-EC) method was developed for the determination of three main chlorogenic acid isomers, namely 3-, 4-, and 5-caffeoylquinic acids (CQA), in coffee leaves aqueous extracts. Samples from eight coffee species, namely; Coffea arabica, Coffea canephora, Coffea liberica, Coffea humilis, Coffea mannii, Coffea charrieriana, Coffea anthonyi, and Coffea liberica var. liberica, were grown and collected in tropical greenhouses. Linearity of the calibration graphs was observed in the range from the limit of quantification to 1.0 × 10−5 M, with R2 equal to 99.9% in all cases. High sensitivity was achieved with a limit of detection of 1.0 × 10−8 M for 3-CQA and 5-CQA (i.e., 3.5 µg/L) and 2.0 × 10−8 M for 4-CQA (i.e., 7.1 µg/L). The chromatographic profile of the samples harvested for each Coffea species was studied comparatively. Obtained raw data were pretreated for baseline variations and shifts in retention times between the chromatographic profiles. Principal Component Analysis (PCA) was applied to the pretreated data. According to the results, three clusters of Coffea species were found. In the water sample extracts, 5-CQA appeared to be the major isomer, and some species contained a very low amount of CQAs. Fluctuations were observed depending on the Coffea species and harvesting period. Significant differences between January and July were noticed regarding CQAs content. The species with the best CQAs/caffeine ratio was identified. The LC-EC data were validated by liquid chromatography-high resolution mass spectrometry (LC-HRMS).

Electrochemical studies of ethoxyquin and its determination in salmon samples by flow injection analysis with an amperometric dual detector

Ethoxyquin (EQ) is an antioxidant widely used in the food industry. Some concerns for human health have been reported since its utilization in animal feed may lead to residues in human food such as salmon samples. This work aimed to investigate the electrochemical behavior of EQ and its major oxidation products namely a dimer of EQ (EQDM) and ethoxyquin quinone imine (EQI) by cyclic voltammetry (CV) at a carbon screen printed electrode (cSPE). The stability of these products and their reactivity against glutathione (GSH) were also studied. Oxidized products and thiol adducts were identified by a microelectrolysis of an EQ solution onto a cSPE in the absence and in the presence of GSH. The products were analyzed off-line, by liquid chromatography coupled to a mass spectrometer (LC-MS). One of the generated product (EQI) was shown to be highly reactive towards GSH. Based on the redox pattern of EQ, a flow injection analysis with a dual cSPE was developed in order to detect in a rapid manner EQ in salmon samples. Since matrix effects were observed, matrix-matched calibration curves with spiked samples were built. A linear response was obtained between 20-100 μM and a limit of detection (LOD) of 7.5 μM (8.2 mg/kg of salmon). Trueness was assessed with recovery assays at three levels of concentration. The recovery was close to 100 %. Precision was determined as RSD (%) with values lower than 6 % in all cases.

Metabolomics fingerprint of coffee species determined by untargeted-profiling study using LC-HRMS

Coffee bean extracts are consumed all over the world as beverage and there is a growing interest in coffee leaf extracts as food supplements. The wild diversity in Coffea (Rubiaceae) genus is large and could offer new opportunities and challenges. In the present work, a metabolomics approach was implemented to examine leaf chemical composition of 9 Coffea species grown in the same environmental conditions. Leaves were analyzed by LC-HRMS and a comprehensive statistical workflow was designed. It served for univariate hypothesis testing and multivariate modeling by PCA and partial PLS-DA on the Workflow4Metabolomics infrastructure. The first two axes of PCA and PLS-DA describes more than 40% of variances with good values of explained variances. This strategy permitted to investigate the metabolomics data and their relation with botanic and genetic informations. Finally, the identification of several key metabolites for the discrimination between species was further characterized.

Liquid chromatography-electrochemical detection for the determination of ethoxyquin and its dimer in pear skin and salmon samples

Ethoxyquin (EQ) is widely used as a synthetic antioxidant in animal feed, an antiscalding agent in apples and pears and as a color preservative in some spices. Since the presence of EQ in food products could cause negative health effects it is necessary to develop reliable analytical methods to evaluate the risk of human exposure. In this work, a sensitive, selective and accurate method based on solid-liquid extraction followed by clean-up with solid sorbent and liquid chromatography-electrochemical detection analysis with boron doped diamond electrode (LC-EC) for the determination of ethoxyquin and its dimer (EQDM) in pear skin and salmon samples, was developed. The method was validated according to the European Commission guidelines. The main variables of extraction were accurately optimized. The amounts of solid sorbents for clean-up procedure were optimized by using experimental design. A Box-Behnken design to obtain the optimum conditions was applied. For validation, a matrix-matched calibration was established and a recovery assay with spiked samples was carried out. The limits of detection (LODs) found were 0.05 and 0.1 mg kg−1 for EQ and its dimer, respectively. The precision (as relative standard deviation, RSD) was lower than 15% with recoveries of compounds close to 100% in spiked samples.

Identification of coffee leaves using FT-NIR spectroscopy and SIMCA

Abundant literature has been devoted to coffee beans (green or roasted) chemical description but relatively few studies have been devoted to coffee leaves. Given the fact that coffee leaves are used for food and medicinal consumption, it was of interest to develop a rapid screening method in order to identify coffee leaves taxa. Investigation by Fourier - Transform near infrared spectroscopy (FT-NIRS) was performed on nine Coffea taxa leaves harvested over one year in a tropical greenhouse of the Botanic Garden Meise (Belgium). The only process after leaves harvesting was an effective drying and a homogeneous leaves grinding. FT-NIRS with SIMCA analysis allowed to discriminate the spectral profiles across taxon, aging stage (mature and senescence coffee leaves) and harvest period. This study showed that it was possible (i) to classify the different taxa, (ii) to identify their aging stage and (iii) to identify the harvest period for the mature stage with a correct classification rate of 99%, 100% and 90%, respectively.

2017

Electrochemical detectors in liquid chromatography: Recent trends in Pharmaceutical and Biomedical Analysis

Liquid chromatography (LC) coupled to an electrochemical (EC) detector is a complementary analytical tool compared to LC coupled with optical or mass spectrometry detectors (LC-MS). LC-EC can be applied to the determination of molecules difficult to be analyzed by other commercially available detectors. New EC detector design and new working electrode material have extended the scope of application in the field of pharmaceutical compounds analysis. Combining EC with LC-MS offers additional advantages compared to optical detectors in terms of drug stability and drug metabolism mimicry studies. Selected literature devoted to pharmacologically active compounds in their dosage forms, herbal drugs in natural products, drug residues in feed and/or in biological samples are reported in this review.

Determination of Three Capsaicinoids in Raw Red Pepers and Seasoning Powders by Liquid Chromatography with Coulometric Detection

The simultaneous determination of three capsaicinoids in raw red pepper and in foods was studied by liquid chromatography coupled to a coulometric detector. The capsaicinoids were separated on an ODS C18 reversed column by isocratic elution with a mobile phase based on acetonitrile −0.15 M acetic acid (51:49%, v/v) at a flow rate of 0.8 mL min−1. The limit of detection (S/N> 3) was 10 pg (injected mass) at an applied potential of 0.650 V vs. Pd. The peak area of the three studied compounds was found to be related to the amount injected from 50 pg to 100 ng range (r=0.999). The relative standard deviation (RSD, n=10) was comprised between 1.5∼4.4 and 1.0∼3.5 % for 100 pg and 5 ng, respectively. The determination of three capsaicinoids in raw red peppers and red pepper containing foods was successfully realized.

A Reduced Graphene Oxide-based Electrochemical DNA Biosensor for the Detection of Interaction between Cisplatin and DNA based on Guanine and Adenine Oxidation Signals

A glassy carbon electrode (GCE) was modified by electrochemically reduced graphene oxide (ERGO) for subsequent dsDNA immobilization. The interaction of cisplatin with dsDNA was studied at this modified electrode. Quantitative investigations were performed by adsorptive transfer stripping voltammetry (AdTSV) using differential pulse voltammetry (DPV). The morphology and structure of graphene oxide (GO) and ERGO modified GCEs (GO/GCE and ERGO/GCE, respectively) were characterized by UV-vis, FT-IR, Raman spectroscopy and cyclic voltammetry. Compared with the bare GCE and the GO/GCE, the ERGO/GCE exhibited excellent electrocatalytic activity towards the oxidation of dsDNA due to guanine and adenine groups, testified by high oxidation peak currents and decreased oxidation potentials. The interaction of micromolar concentrations of cisplatin with surface confined dsDNA was readily detected as inferred from the decrease of the voltammetric oxidation peaks of guanine and adenine. This trend was significantly greater at the ERGO/GCE compared to the GO/GCE. The interaction of cisplatin with dsDNA was also studied in solution phase by AdTSV with detection at the ERGO/GCE.

Application of a tyrosinase microreactor - detector in a flow injection configuration for the determination of affinity and dynamics of inhibitor binding

An original self-contained enzymatic microreactor − detector in a thin layer flow-through configuration has been developed for the screening of tyrosinase inhibitors. The microreactor- detector consisted of a gold disk for tyrosinase immobilization adjacent to a glassy carbon disk as working electrode (GCE). Using L-tyrosine as substrate, the enzymatic product formed (dopaquinone) was detected amperometrically at the GCE. Experimental parameters most affecting the L-tyrosine response were optimized with a central composite design. Measurements were performed in phosphate buffer pH 6.0 with an applied potential of +50 mV vs Ag/AgCl and a flow rate of 100 μL/min. The determined Kmapp was 1.9 ± 0.1 mM. The setup permitted the determination of the efficiency and the duration of inhibition of twelve compounds known as tyrosinase inhibitors namely kojic acid, gallic acid, azelaic acid, benzoic acid, L-ascorbic acid, hydroquinone, glabridine, resveratrol, quercetin dihydrate, captopril, L-cysteine and L-glutathione reduced. L-Ascorbic acid and kojic acid were found to be the most potent inhibitors for the two studied criteria with IC50 of 32 μM and 156 μM, respectively.

2016

Determination of Thiols and Free Thiol Content in a Protein with Liquid Chromatography Coupled to Amperometric Detection at a Silver Based Carbon Paste Electrode

Liquid chromatography (LC) coupled to an electrochemical detector was applied for the determination of small thiols such as cysteine (Cys), glutathione (GSH) and dithiothreitol (DDT) and the free thiol content in a protein. The thio-compounds were first derivatized by 2,2′-dipyridyldisulfide (DPDS) at pH 4.5 to yield the corresponding disulfide and 2-thiopyridone (2-TP). The reaction mixture was separated isocratically on a reversed-phase C18 column with amperometric detection (AD) at a carbon paste electrode modified with silver microparticles and polarized at 0.080 V versus Ag/AgCl. The LC-AD response corresponding to the generated 2-TP allowed for the indirect determination of the studied thiol derivatives in the 1×10−5-1×10−4 M range for Cys and GSH and 5×10−6-5×10−5 M range for DTT. The LOD and LOQ values were in the range of 9×10−7-4×10−6 M and 3×10−6−-5.5×10−6 M, respectively for the three studied compounds. Application to the determination of the free thiol content of human and bovine serum albumin as model proteins was realized. The LC-AD results were validated with respect to a developed spectrophotometric method performed under identical experimental derivatization conditions.

Determination of groundwater mercury (II) content using a disposable gold modified screen printed carbon electrode

Mercury (II) measurements were performed thanks to a newly developed electrochemical method using a disposable gold modified screen printed carbon electrode. The method has a wide dynamic range (1-100 μg/L), a good accuracy and a limit of detection in compliance with WHO standards. The application of the method to several groundwater samples made it possible to identify, for the first time, mercury content higher than the recommended WHO standard value in a gold mining activity area in the northern part of Burkina Faso. The accuracy of the assay was checked by ICP/MS.

Determination of the anticancer drug sorafenib in serum by adsorptive stripping differential pulse voltammetry using a chitosan/multiwall carbon nanotube modified glassy carbon electrode

Adsorptive stripping differential pulse voltammetry (AdSDPV) was applied to the assay of sorafenib in human serum sample. Cyclic voltammetry at a carbon based screen printed electrode (SPE) permitted to detect the irreversible oxidation of SOR with formation of a new compound reversibly oxidized at a lower potential. Quantitative assays were realized using a chitosan/carboxylic acid functionalized multiwalled carbon nanotube modified glassy carbon electrode in 0.1M phosphate buffer pH7.0 in the presence of 50% methanol. The AdSDPV method provided two linear responses within the concentration ranges 1×10-8-8×10-8M and 1×10-7-8×10-7M in serum with LOQ and LOD of 3.2×10-9 and 9.6×10-10 of lower linear range, respectively. The recovery of sorafenib in spiked serum was 97.5%.

Antibodies as target for affinity biosensors

Antibodies or immunoglobulins (Ig) are proteins produced by the immune system to protect the body by identifying and neutralizing pathogens. The determination of antibodies is an important area in bioanalysis because their presence provides information about pathologies such as infections, allergies, auto-immune diseases and cancers. Antibodies can be readily detected and quantified by using immunosensors. This review provides an up-to-date overview of immunosensors for the determination of antibodies which can be implemented in the clinical area, for point-of care applications or in routine laboratories.

2015

Contribution of Electrochemistry to the Biomedical and Pharmaceutical Analytical Sciences.

All analytical techniques have experienced major progress since the last ten years and electroanalysis is also involved in this trend. The unique characteristics of phenomena occurring at the electrode-solution interface along with the variety of electrochemical methods currently available allow for a broad spectrum of applications. Potentiometric, conductometric, voltammetric and amperometric methods are briefly reviewed with a critical view in terms of performance of the developed instrumentation with special emphasis on pharmaceutical and biomedical applications.

Électrochimie analytique: Potentiels et limitations

Analytical techniques are all facing major progress these last ten years and electroanalysis is also involved in this trend. The unique characteristics of the phenomenon occurring at the electrode-solution interface along with the variety of electrochemical methods allow for a broad spectrum of applications. Potentiometric, conductimetric, voltamperometric and amperometric methods are briefly reviewed with a critical view in terms of performances of the developed instrumentation and of application domains.

An experimental design approach to optimize an amperometric immunoassay on a screen printed electrode for Clostridium tetani antibody determination.

An immunoassay for the determination of anti-tetani antibodies has been developed using a screen printed electrode (SPE) as solid support for toxoid (antigen) immobilization. The assay was performed in guinea pig serum. The immunoreaction and the subsequent amperometric detection occurred directly onto the SPE surface. The assay consisted of spiking the anti-tetani sample directly onto the toxoid modified SPE, and then a second antibody, i.e. a HRP-labeled anti-immunoglobulin G, was deposited onto the biosensor. Subsequent amperometric detection was realized by spiking 10µL of a hydroquinone (HQ) solution into 40µL of buffer solution containing hydrogen peroxide. An experimental design approach was implemented for the optimization of the immunoassay. The variables of interest, such as bovine serum albumin (BSA) concentration, incubation times and labeled antibody dilution, were optimized with the aid of the response surface methodology using a circumscribed central composite design (CCCD). It was observed that two factors exhibited the greatest impact on the response, i.e. the anti-tetani incubation time and the dilution factor of the labeled antibody. It was discovered that in order to maximize the response, the dilution factor should be small, while the anti-tetani antibody incubation time should be long. The BSA concentration and the HRP-anti-IgG incubation had very limited influence. Under the optimized conditions, the immunoassay had a limit of detection of 0.011IU/mL and a limit of quantification of 0.012IU/mL. These values were below the protective human antibody limit of 0.06IU/mL.

Liquid Chromatography with Amperometric Detection at a Silver Based Detector for the Determination of Thiocompounds: Application to the Assay of Thiopurine Antimetabolites in Urine

(Graph Presented). A silver amperometric detector coupled to liquid chromatography (LC) was used for the determination of 6-thioguanine (6-TG) and two of its metabolites, thiouric acid (TU) and 2-amino-6-mercaptopurine riboside (6-TGR). The silver detector coupled to LC operated at a low applied potential (0.08 V vs Ag/AgCl) and offered a chromatogram with peak responses corresponding to molecules interacting with silver, namely, chloride ions and small soluble biothiols in addition to the organothiol drug compounds investigated. Online electrochemical surface cleaning permitted the improvement of the repeatability and peak shape of the recorded signal compared to direct current amperometric detection (AD) when operating in chloride containing media. The studied molecules were eluted isocratically within 5 min on a reversed-phase C18 column without interference from endogenous biothiols present in urine samples. Diluted urine samples (1:1) were directly injected in the LC setup; a linear calibration curve was obtained between peak area and analyte concentration between 0.1 and 10 μM for all the studied molecules. Limits of detection (LODs) were 0.03, 0.008, and 0.01 μM, and the limits of quantification (LOQs) were 0.1, 0.02, and 0.03 μM for TU, 6-TG, and 6-TGR, respectively. Within-day RSDs were 2%, 0.8%, and 1% and between-day RSDs were 2%, 0.9%, 2% for TU, 6-TG, and 6-TGR, respectively. Recoveries in spiked urine were 99.8%, 99.9%, and 99.0% for TU, 6-TG, and 6-TGR, respectively.

Determination of arsenic (III) at a nanogold modified solid carbon paste electrode

A selective and sensitive electroanalytical method was developed for arsenic determination based on a nanogold (AuNP) modified solid carbon paste working electrode (SCPE) modified in two steps (i) physisorption and (ii) additional electrodeposition of nanogold particles in the presence of iodide. Copper(II) interference was solved by covering the gold layer by a self assembled mono layer (SAM) of glutathione. Using DPASV a linear response of the signal was obtained as a function of As(III) in the concentration range 0.05-20μM (4-1498ppb) with a limit of detection of 0.01μM (0.9ppb). Sample stirring and degassing were not needed. Application to the determination of arsenic(III) and (V) in underground water samples from Burkina Faso was successfully achieved.

2014

Flow-through enzyme immobilized amperometric detector for the rapid screening of acetylcholinesterase inhibitors by flow injection analysis.

A commercially available thin-layer flow-through amperometric detector, with the sensing block customized in an original design, was applied to the screening of drug compounds known as acetylcholinesterase (AChE) inhibitors. AChE from electric eel was covalently immobilized onto a cysteamine modified gold disk adjacent to a silver disk working electrode. On-line studies were performed by flow injection analysis (FIA) in PBS buffer pH 7.4. Seven commercially available AChE inhibitors used in the medical field, namely neostigmine, eserine, tacrine, donepezil, rivastigmine, pyridostigmine and galantamine as well as two natural compounds, quercetin and berberine, were investigated. The same trend of inhibitory potency as described in the literature was observed. Of particular interest and in addition to the determination of the IC50 values, this flow-through system allowed the study of both, the stability of the enzyme-inhibitor complex and the kinetic of the enzyme activity recovery.

Nanoimmunoassay onto a screen printed electrode for HER2 breast cancer biomarker determination

A chip format sandwich-type immunoassay based on Nanobodies® (Nbs) with the Human Epidermal Growth Factor Receptor (HER2) extracellular domain as antigen model has been developed. The HER2 is considered as an important biomarker because its overexpression causes an aggressive type of breast cancer. Nbs are single domain antigen-binding fragments derived from camelid heavy-chain antibodies. The strategy of the presently developed sandwich immunoassay takes advantage of the small size of Nbs for the detection of the electroactive redox tracer onto the screen printed electrode (SPE). A capture anti HER2 Nb was covalently immobilized onto the SPE, and the detection Nb, raised against another epitope of HER2, was labeled with horseradish peroxidase (HRP). The biosensor signal corresponded to the electroreduction of para-quinone generated at the SPE by the HRP in the presence of hydroquinone and hydrogen peroxide. The best performing and optimized immunoassay conditions consisted of 2 and 20 min for the first and the second incubation times, respectively. The amperometric signal obtained was proportional to the logarithm of HER2 concentration between 1 and 200 μg/mL and the modified SPE storage stability lasted for at least three weeks. Determination of HER2 in human cells has been realized. © 2014 Elsevier B.V.

A new chemical criteria for white wine: The glutathione equivalent capacity

The present work aimed at showing the interest in applying liquid chromatography with amperometric detection at a silver electrode (LC-EC-Ag) in order to record a chromatogram highly selective to non volatile aminothiols present in white wines. By integrating and summing the peak area of the aminothiols and by normalizing with respect to the peak area of an injected standard solution of glutathione (1 μM) a new quantitative criteria for white wine characterization is proposed namely, the glutathione equivalent capacity (GEC). The LC setup uses a C18 column in isocratic mode and the analysis takes less than 4 min. The wine sample needs no sample treatment other than dilution with the mobile phase. This new methodology and concept is illustrated by the LC-EC-Ag analysis of several white wines of different origins especially Alsace Riesling wines and Riesling grape juice. It is anticipated that in addition to the determination of the GEC, the developed method may be of interest for establishing a white wine "signature" based on the chromatographic profile. © 2013 Elsevier Masson SAS. All rights reserved.

Inhibition of myeloperoxidase activity by the alkaloids of Peganum harmala L. (Zygophyllaceae).

Seeds and aerial parts of Peganum harmala L. (Peganum harmala) are widely used in Algeria as anti-inflammatory remedies. Evaluation of Peganum harmala total alkaloids extracts and pure β-carboline compounds as an anti-inflammatory treatment by the inhibition of an enzyme key of inflammatory, myeloperoxidase (MPO) and HPLC quantification of the alkaloids from the different parts of plant.

2013

Differential Pulse Voltammetric Determination of Montelukast in Tablets and Human Plasma by Using Chitosan Modified Carbon Paste Electrode

Electrochemical reduction and determination of montelukast (MKS) was studied in methanol - 0.1M HCl solution (1:1, v/v) by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) at chitosan modified carbon paste electrode. The linear range was 1.70×10-7-1.83×10-5M for DPV analysis. Limit of detection (LOD) and limit of quantification (LOQ) were 5.32×10-8M and 1.61×10-7M, respectively. The developed method was successfully applied to the determination of MKS in tablets and spiked human plasma. The results obtained were in good agreement with those obtained using a reported spectrofluorimetric technique. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of aminothiols by liquid chromatography with amperometric detection at a silver electrode: Application to white wines

Liquid chromatography coupled to a silver electrode based flow-through amperometric detector (LC-EC-Ag) was developed for the determination of aminothiols in white wines. The C18 reversed phase LC system operated in the isocratic mode at 0.7mLmin-1 and used an acidic mobile phase composed of formic acid, EDTA, sodium nitrate, sodium hydroxide, and methanol 1% (v/v) at pH 4.5. The working electrode operated at 0.08V vs Ag/AgCl, 3M KCl and its manual cleaning was realized once a month by smoothing on a polishing cloth. The analyzed aminothiols were resolved and eluted within 4min, and all standard curves were linear in the range 2×10-7-2×10-5M. The analyzed wine samples needed no preparation other than dilution with the mobile phase. The concentration of cysteine (CYS), homocysteine (HCYS), glutathione (GSH) and N-acetylcysteine (NAC) in bottled white wines, determined by the method of standard addition, was found to be in the low μM range (0.2-2mgL-1) depending on the wine type and its age. © 2013 Elsevier B.V.

Development of an acetylcholinesterase immobilized flow through amperometric detector based on thiocholine detection at a silver electrode

This paper describes the use of a commercially available thin-layer flow through a detector with the sensing block customized in an original design for acetylcholinesterase (AChE) immobilization and suitable for inhibition studies by flow injection analysis (FI). AChE was chemically linked onto a gold disk substrate adjacent to a silver disk electrode. The downstream positioned silver electrode, poised at 0.08 V vs. Ag/AgCl, KCl 3 M, permitted the sensitive amperometric detection of liberated thiocholine (TCh) using acetylthiocholine (ATCh) as enzyme substrate. A typical Michaelis-Menten curve was obtained for ATCh within the concentration range 1 × 10-5-1 × 10 -2 M with a Kmapp of 5.93 × 10-4 M. ATCh quantification was achieved with a limit of detection (LOD) of 5.3 × 10-6 M. The utility of the developed FI setup was demonstrated for AChE inhibition studies using neostigmine as model compound. The IC50 for neostigmine was obtained to be 1.45 × 10-7 M. © 2013 Elsevier B.V. All rights reserved.

Design, synthesis, and structure-activity relationship studies of novel 3-alkylindole derivatives as selective and highly potent myeloperoxidase inhibitors.

Due to its production of potent antimicrobial oxidants including hypochlorous acid, human myeloperoxidase (MPO) plays a critical role in innate immunity and inflammatory diseases. Thus MPO is an attractive target in drug design. (Aminoalkyl)fluoroindole derivatives were detected to be very potent MPO inhibitors; however, they also promote inhibition of the serotonin reuptake transporter (SERT) at the same concentration range. Via structure-based drug design, a new series of MPO inhibitors derived from 3-alkylindole were synthesized and their effects were assessed on MPO-mediated taurine chlorination and low-density lipoprotein oxidation as well as on inhibition of SERT. The fluoroindole compound with three carbons in the side chain and one amide group exhibited a selectivity index of 35 (Ki/IC50) with high inhibition of MPO activity (IC50 = 18 nM), whereas its effect on SERT was in the micromolar range. Structure-function relationships, mechanism of action, and safety of the molecule are discussed.

Foodomics platform for the assay of thiols in wines with fluorescence derivatization and ultra performance liquid chromatography mass spectrometry using multivariate statistical analysis

The presence of specific volatile and aminothiols in wine is associated with quality, worth, price, and taste. The identification of specific thiol-containing compounds in various wines has been reported in many valuable and interesting works. In this study, a novel foodomics assay of thiol-containing compounds, such as free aminothiols and related conjugates, was developed using ultra performance liquid chromatography (UPLC) with fluorescence (FL) and electrospray (ESI) time-of-flight mass spectrometric (TOF/MS) detections. FL specific derivatization was applied along with multivariate statistical analysis. First, the optimal experimental conditions were studied using representative thiols, such as l-cysteine, N-acetyl-l-cysteine, cysteamine, and l-glutathione, and then the UPLC-FL derivatization and separation steps were fixed for the subsequent screening of unknown thiol-containing compounds. The screening assay consisted of monitoring the UPLC-TOF/MS peaks of unknown thiols, which decreased due to the derivatization as compared to the nonderivatized thiols. The principal component analysis of the UPLC-TOF/MS data could be well-differentiated and categorized into two groups. The orthogonal signal correction partial least-squares discriminant analysis, the so-called S-plot, showed that the quality differentiation is directly related to the decrease of native thiols and increase of derivatized thiols. With this strategy, the mass difference from the derivatization reagent (+m/z 198) could be utilized for the identification of these thiols using the FL peaks retention time and metabolomics-databases. The presence of l-glutathione in rice wine was for the first time reported on the basis of the available metabolomics-databases and standard matching. This novel concept based on foodomics could be applied in food analysis for the ready screening of specific functional compounds by exploiting the various derivatization modes available. © 2013 American Chemical Society.

2011

Utility of screen printed electrodes for in vitro metabolic stability assays: Application to acetaminophen and its thioconjugates

Tyrosinase immobilized magnetic nanobeads for the amperometric assay of enzyme inhibitors: application to the skin whitening agents.

The immobilization of tyrosinase onto glutaraldehyde activated streptavidine magnetic particles and subsequent retention onto a magnetized carbon paste electrode for the amperometric assay of tyrosinase inhibitors is described. Tyrosine was used as substrate as it is the first substrate in the melanogenesis process. The sensing mode is based on monitoring the decrease of the amperometric signal corresponding to the electrochemical reduction of dopaquinone enzymatically generated. This current decrease is due to the presence of inhibitors acting directly on the enzyme or inhibitors acting on the product of the enzymatic reaction, i.e. dopaquinone. The methodology is designed for the evaluation of the inhibitory potency of the most frequently used active substances in cosmetic marketed products against hyperpigmentation such as kojic acid, azelaic acid and benzoic acid. These compounds bind to the tyrosinase active center. Ascorbic acid is also investigated as it interrupts the synthesis pathway of melanin by reducing the melanin intermediate dopaquinone back to l-dopa. By comparing the obtained IC(50), under the same experimental conditions, the order of their inhibitory potency was: kojic acid (IC(50)=3.7 × 10(-6)M, K(i)=8.6 × 10(-7)M), ascorbic acid (IC(50)=1.2 × 10(-5)M), benzoic acid (IC(50)=7.2 × 10(-5)M, K(i)=2.0 × 10(-5)M) and azelaic acid (IC(50)=1.3 × 10(-4)M, K(i)=4.2 × 10(-5)M) in close agreement with literature spectrophotometric inhibition data using the soluble tyrosinase.

Simultaneous determination of acetaminophen (paracetamol) and ascorbic acid in pharmaceutical formulations by LC coupled to a screen printed carbon based amperometric detector.

The assay of acetaminophen (APAP) and ascorbic acid (AA) was performed by liquid chromatography (LC) with amperometric detection at a screen printed carbon based electrode poised at +0.6 V versus Ag pseudoreference electrode. A microparticle based conventional RP-C18 and a monolithic RP-C18 column were studied comparatively for the analytes separation using a mobile phase based on 0. 1 M phosphate buffer-methanol 91:9 (v/v) at pH 6.5. The linear calibration range for both compounds was comprised within 2×10-7-1×10-4 M. Limit of detection (LOD) for APAP and AA was 2×10-7 and 5×10-7 M, respectively and the limit of quantification (LOQ) was 5. 10-7and 1×10-6 M, respectively. Square wave voltammetry at a Nafion modified glassy carbon electrode was developed and applied to the determination of APAP in order to validate the results obtained by the monolithic LC method for drug formulations. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

2010

Enzyme immobilized magnetic nanoparticles for in-line capillary electrophoresis and drug biotransformation studies: application to paracetamol.

Enzyme Immobilized Magnetic Nanoparticles (EMNPs) were injected and magnetically retained, as a microreactor, in the capillary of a capillary electrophoresis (CE) setup with UV detection. The enzyme horseradish peroxidase (HRP) was chemically immobilized onto commercially available magnetic 300 nm diameter nanoparticles. Paracetamol (acetaminophen: N-acetyl-p-aminophenol), a common analgesic drug, was used as model drug compound. The enzymatic reaction was studied in-line by CE in 12.5 mM phosphate buffer pH 7.4 containing 20 mg/ml sulfated- beta -cyclodextrin and 0.1 mM hydrogen peroxide. By means of the developed setup, the apparent Michaelis Menten constant between HRP and acetaminophen (APAP) was determined as K(m)(app) = 53+/-5 microM. This approach was found to be of interest for enzyme kinetics studies with short time resolution condition. Based on our results and from literature data, it was possible to infer that the in-line generated product was an APAP dimer. Higher enzyme immobilized beads loading in the CE setup generated the APAP dimer with two additional minor peaks likely attributed to APAP trimer and tetramer. N-acetyl-p-benzoquinone imine (NAPQI) was not generated during APAP short time migration through the in-line microreactor.

The effects of excipients on transporter mediated absorption.

Traditionally most pharmaceutical excipients used for peroral dosage forms have been considered to be inert, although they have been known to play an important role in governing the release of the active pharmaceutical ingredient (API) required for the desired therapeutic effect. Of considerable interest is the emerging data demonstrating that many of these "inert" excipients may produce subtle changes that could directly or indirectly alter the activity of membrane-spanning proteins such as transporters. In this way, excipients could be altering the overall ADMET properties of an incorporated drug thereby affecting its intended therapeutic efficacy and/or enhancing adverse side effects. Therefore, given this recent evidence, it seems necessary to review what has been reported in the literature on interactions of excipients with human physiological entities, particularly transporters. As of today, safety/toxicity evaluations are typically based on the appearance of gross morphological changes rather than the effects on a cellular level, the ability of excipients in modifying the pharmacological activity of an active drug could lead to toxicity evaluation in routine for each additive used in oral formulations. Further knowledge on this subject will enable formulators to make more rational decisions in dosage form design and will help answer the question of whether certain excipients should be considered active pharmaceutical components of formulations.

Anti-Clostridium tetani antibody determination in serum samples by amperometric immunosensing

Comparative study of the determination of parabens in shampoos by liquid chromatography with amperometric and coulometric detection

The simultaneous determination of four para-hydroxybenzoic acid esters (parabens) in shampoos was studied by liquid chromatography (LC) with amperometric (LC-AD) and coulometric (LC-CD) detection. The parabens were separated on an ODS C18 reversed column by isocratic elution with a mobile phase based on methanol-0.1M acetic acid (60:40%, v/v) with 0.02M NaClO4 at a flow rate of 0.8 mL min-1. The limit of detection (S/N>3) for the analytes was in the 15 -25 pg (injected mass) range at an applied potential of 1.20 V vs. Ag/AgCl using the LC-AD and in the 2 -3 pg range at a potential of 0.790 V vs. Pd using the LC-CD. The peak ratio of the internal standard peak (IS: 4-hydroxybenzoic acid secbutyl ester) versus the analyte peak was found to be related to the amount injected from 0.1 ng to 100ng (r=0.996 -0.999) with the LC-AD and from 0.050 ng to 100 ng range (r=0.999 -1.000) with the LC-CD. The relative standard deviation (RSD, n=10) was comprised between 1.8 to 3.5% by LC-AD (5 ng injected) and between 2.0 to 2.4% by LC-CD (0.5 ng injected). The determination of four most used parabens in ten different shampoos was successfully realized. © 2010 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.

2009

Improving the spectrophotometric determination of the alkylating activity of anticancer agents: a new insight into the mechanism of the NBP method.

In this paper, the mechanism of the nitrobenzylpyridine (NBP) method to measure the alkylating activity of drugs originally described by Epstein et al. [J. Epstein, R.W. Rosenthal, R.J. Ess, Anal. Chem. 27 (1955) 1435-1439] and modified later by others was revisited using melphalan, m-sarcolysin, chlorambucil, cyclophosphamide and ifosfamide. Its direct application to determine the activity of these drugs in human serum and aqueous media is described and discussed. This method, based on the formation of a chromophore due to the reaction between the alkylating agent and NBP, was significantly improved by extracting as quickly as possible the reaction product(s) into chloroform before adding alkali to develop the color. This significantly limited the degradation by hydrolysis of the products and enhanced the yield of the end chromophore in the organic phase. The reaction time was optimized by monitoring each compound color development. The best reaction time for each compound was selected and a higher stability of the extracted color over at least 1h was obtained (compared to a couple of minutes in previous studies). Most interestingly, water evaporation due to heating had little or no effect on the linearity of standard curves evaluated in the micromolar concentration range. Both the sensitivity and reproducibility of the method were therefore significantly improved. There appears to be a direct correlation between compound hydrolysis and alkylation activity; the relative reactivity is different among the compounds owing to the rate of (i) production, (ii) the relative proportions and (iii) the hydrolysis of the intermediates. A general mechanism for the nucleophilic competitive substitution is proposed.

2008

A novel transport and delivery mechanism underpins the effectiveness of prolyl-m-sarcolysyl-p-fluorophenylalanine (PSF) in a human melanoma xenograft nude-mouse model.

The alkylating peptide PSF shows very promising results in vitro on different cancer cells but its efficacy in animals has not been assessed. Here we evaluate the efficacy of PSF in human melanoma-bearing nude mice and examine the underlying mechanism. In melanoma-bearing nude mice, escalating doses of PSF showed dose-dependent responses and reached tumor regression with an optimal dose of 20 mg/kg for 1 month. A comparison of PSF with its free moiety m-sarcolysin and melphalan showed a highly significant advantage of PSF. Furthermore, dose fractionation yielded an even better control of tumor regrowth. In vitro studies unraveled an original delivery mechanism based on the rapid binding of PSF mainly due to red blood cells to form a pro-drug complex and the subsequent release of active metabolites by tumor-associated proteolytic enzymes. Blood kinetics showed one major metabolite partially released over time, while in the presence of melanoma cells three additional metabolites are generated. Interestingly, tumor-shed proteases also induce the production of these metabolites and varying combinations of enzyme inhibitors indicate the involvement of metallo- and other families of proteases in the delivery process. This particular transport and delivery of such an alkylating agent may have several benefits, mainly lowering the drug-free moiety in plasma and at the same time increasing its concentration in protease rich areas such as tumors.

Highly sensitive determination of iodide by ion chromatography with amperometric detection at a silver-based carbon paste electrode.

A silver-based solid carbon paste electrode was developed for use as a detector in ion chromatography (IC) for the sensitive determination of iodide in real samples. Micro- and nano-particles of silver were investigated for the fabrication of different electrodes. The iodide assay was based on IC with amperometric detection (IC-AD) at a silver composite electrode polarized at +0.080 V versus Ag/AgCl. Free iodide and organoiodide compounds were studied. The detection process was characterized by studying the redox behavior of iodide ions at both silver and silver composite electrodes by cyclic voltammetry (CV). The presence of iodide ions in solution was found to considerably facilitate metallic silver oxidation, with response currents directly related to iodide concentration. The calibration curve at the selected silver carbon paste electrode was linear in the concentration range comprised between 0.635 microg/L and 63.5 microg/L iodide. The relative standard deviation (R.S.D.) for successive injections was below 3% for all iodide standard solutions investigated. The limit of detection (LOD) was 0.47 microg/L (3.7 nmol/L) for an injection volume of 20 microL, i.e. 74 fmol injected. The IC-AD method was successfully applied to the determination of iodide in complex real samples such as table salts, sea products and iodide bound drug compounds. The analytical accuracy was verified by the assay of iodide in milk powder from an iodide certified reference material (CRM) Community Bureau of Reference (BCR) 150.

2007

Development of amperometric horseradish peroxidase based biosensors for clozapine and for the screening of thiol compounds

Two amperometric biosensors with immobilized horseradish peroxidase (HRP) were developed for the investigation of the clozapine drug oxidation and for thiols screening based on biosensor signal inhibition. The HRP was retained either in magnetized nanoporous silica microparticles (MMPs) or in a carbon paste (CP). The latter served for the carbon paste electrode while the MMPs were attracted in close proximity of a magnetized carbon electrode. The potential use of these configurations for drug oxidation and inhibition studies was illustrated by the enzymatic oxidation of clozapine (CLZ) in the presence of hydrogen peroxide. The biosensor signal corresponded to the electro-reduction of CLZ oxidation products namely a nitrenium ion (CLZox) generated by the enzyme HRP. Several thiols reactive towards CLZox were investigated and the biosensor signal inhibition (IC(50)) was comparatively determined. A protective effect of the nanoporous silica and carbon paste matrices towards HRP inactivation was inferred by comparing the biosensor inhibition results with those obtained with the free enzyme in solution.

Determination of dye precursors in hair coloring products by liquid chromatography with electrochemical detection

The simultaneous determination of seven aminophenols, resorcinol and p-phenylenediamine in hair coloring products was performed by liquid chromatography (HPLC) with amperometric detection (ED). The aminophenols were separated on a ODS C18 reversed-phase column by isocratic elution with a mobile phase based on 0.1 M acetate buffer pH 4.5-methanol (90:10%, v/v) at a flow rate 0.8 mL min(-1). The limit of detection (S/N=3) for the aminophenols was in the 15-40 pg (injected mass) range at an applied potential of 0.950 V versus Ag/AgCl. Peak heights for the aminophenols and the two others compounds were found to be linearly related to the amount injected, from 0.3 to 300 ng (r>0.994-0.999). The relative standard deviation (R.S.D., n=10) for 1 ng injected was comprised in the range from 2.5 to 6.2%, depending on the aminophenol tested. The present method minimizes troublesome and time-consuming pretreatment procedures and it was applied to the determination of aminophenols, resorcinol and phenylenediamine in hair coloring formulations.

2006

Amperometric biosensor based on horseradish peroxidase immobilised magnetic microparticles

Magnetised silica-based microparticles (MMPs) (5 μm) with a high density of nanopores were used for horseradish peroxidase (HRP) immobilization and amperometric biosensor development in batch conditions. The resulting biosensor was applied to study the peroxidation of clozapine (CLZ) which is a dibenzoazepine drug often used in the treatment of neurological disorders. The amperometric response corresponded to the electroreduction of CLZ-oxidized products namely a nitrenium cation and quinoneimine derivative of CLZ. Despite a relatively low amount of immobilized HRP (0.3 μmol/g), clozapine quantification in the micromolar concentration range was achieved by the use of a magnetized solid paraffin carbon paste electrode for microparticles attraction. Diffusion of substrate and products of the enzyme reaction within the nanopores were identified as limiting factors in the biosensor response. This amperometric biosensor configuration has number of interesting advantages such as ease and reproducible microparticle layer renewing, low enzyme consumption, controlled surface immobilization, protective enzyme microenvironment etc. © 2005 Elsevier B.V. All rights reserved.

Amodiaquine polymeric membrane electrode

The construction and electrochemical response characteristics of two types of poly(vinyl chloride) (PVC) membrane sensors for the determination of amodiaquine hydrochloride (ADQ.2HCl) are described. The sensing membrane comprised an ion-pair formed between the cationic drug and sodium tetraphenyl borate (NaTPB) or potassium tetrakis(4-chlorophenyl) borate (KTCPB) in a plasticized PVC matrix. Eight PVC membrane ion-selective electrodes were fabricated and studied. Several plasticizers were studied namely, dioctyl phthalate (DOP), 2-nitrophenyl octyl ether (NPOE), dioctyl phenylphosphonate (DOPP) and bis(2-ethylhexyl)adipate (EHA). The sensors display a fast, stable and near-Nernstian response over a relative wide ADQ concentration range (3.2 x 10(-6) to 2.0 x 10(-2) M), with slopes comprised between 28.5 and 31.4 mV dec(-1) in a pH range comprised between pH 3.7 and 5.5. The assay of amodiaquine hydrochloride in pharmaceutical dosage forms using one of the proposed sensors gave average recoveries of 104.3 and 99.9 with R.S.D. of 0.3 and 0.6% for tablets (Malaritab) and a reconstituted powder containing ADQ.2HCl, respectively. The sensor was also used for dissolution profile studies of two drug formulations. The sensor proved to have a good selectivity for ADQ.2HCl over some inorganic and organic compounds, however, berberine chloride interfered significantly. The results were validated by comparison with a spectrophotometric assay according to the USP pharmacopoeia.

Characteristics of new composite- and classical potentiometric sensors for the determination of pharmaceutical drugs

The characteristics of new types of coated wire potentiometric sensors based on composite coatings were compared with classical potentiometric sensors. The composite sensors contained respectively the clay montmorillonite (MM) and the zeolite NaY as the ionically conducting components, embedded in PVC based rubber phase membranes. The behavior of 20 basic medicinal drugs and 5 biogenic amines was studied on 9 potentiometric sensors of different composition. The behavior of 3 composite sensors, and 6 more classical PVC based sensors either of the "inner solution" or "coated wire" type were studied. The analytes were chosen to cover a wide log P range of, e.g. -1.54 (noradrenaline) up to +5.55 (promethazine). All sensors were tested using a high-throughput FIA-based method. The results were interpreted via statistical data analysis. The responses of all electrodes had a very high correlation to the log P of the analytes. This was also the case for the ion-pair based electrodes containing a specific cationic drug as the counterion. Classical ion-pair based sensors containing tetrakis (p-chlorophenyl) borate (TCPB) and a counterion with a high log P value (e.g. promazine) were the least sensitive. The composite-based sensors were the most sensitive. Coated wire electrodes were statistically shown to behave in the same way (selectivity and sensitivity) as inner solution electrodes. The results are discussed using a physico-chemical model. Practical applications of the most performant (composite) sensors are shown in HPLC detection of the pharmaceutical drugs and the biogenic amines. Detection limits in the 10-7 M regio (injected concentrations) are obtained for lipophilic drugs (log P > 2). © 2006 Elsevier Ltd. All rights reserved.

A peroxidase-based biosensor supported by nanoporous magnetic silica microparticles for acetaminophen biotransformation and inhibition studies

Magnetized nanoporous silica based microparticles (MMPs) were used for horseradish peroxidase (HRP) immobilization and applied for amperometric peroxidase-based biosensor development. A magnetized carbon paste electrode permitted the MMPs attraction. The biosensor was applied to the investigation of the enzymatic oxidation of acetaminophen (paracetamol). The biosensor operated at low applied potential and the signal corresponded to the electroreduction of N-acetylbenzoquinoneimine (NAPQI) generated by the enzyme HRP in the presence of hydrogen peroxide. The biosensor allowed performing the quantitation of acetaminophen in the micromolar concentration range and the comparative study of thiols which inhibited the biosensor response. Distinct inhibition results were observed for HRP entrapped in the silica microparticles compared to the soluble HRP. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

Development of an amperometric enzymatic biosensor based on gold modified magnetic nanoporous microparticles

2005

Prediction of clozapine metabolism by on-line electrochemistry/liquid chromatography/mass spectometry

Combining electrochemical conversion, liquid chromatography and electrospray ionization mass spectrometry (EC/LC/ESI-MS) on-line allows the rapid identification of possible oxidation products of clozapine (CLZ) in the absence and in the presence of glutathione. CLZ is, depending on the applied potential, oxidized to various products in an electrochemical flow-through cell using a porous glassy carbon working electrode. Several hydroxylated and demethylated species are detected on-line using LC/MS. While hydroxy-CLZ is most abundant at a potential of 400 mV, demethylation occurs more readily at higher potentials (at around 700 mV versus Pd/H(2) reference). In the presence of glutathione (GSH), various isomeric glutathione adducts and respective products of further oxidation can be identified. The thioadducts are characterized by tandem MS. Mono-GSH and bis-GSH derivatives can be seen in the chromatograms. The results correlate well with the cyclic voltammetric profile of CLZ. The data are relevant from a pharmacological point of view, since similar metabolites (phases I and II) have been reported in the literature. The EC/LC/MS and EC/MS methods should be valuable tools that can be used to anticipate and understand the metabolization patterns of molecules of pharmacological interest and to point out reactive intermediates.

Electrochemical, chemical and enzymatic oxidations of phenothiazines

Biosensors in drug discovery and drug analysis

Biosensors are, by definition, sensing devices comprising a biological component (enzyme, antibody, animal or plant cell, oligonucleotide, lipid, microorganisms, etc.) intimately connected to a physical transducer (electrode, optical fiber, vibrating quartz, etc.). This dual configuration permits a quantitative study of the interaction between a drug compound and an immobilized biocomponent. Ideally, biosensors should be readily implemented and allow for low reagent and energy consumption. Enzyme-based biosensors can be applied in the pharmaceutical industry for monitoring chemical parameters in the production process (in bioreactors). Affinity biosensors are suitable for high-throughput screening of bioprocess-produced antibodies and for candidate drug screening. They are suitable for selective and sensitive immunoassays in clinical laboratories and for decentralized detection of drug residues. Enzyme-based biosensors may be used in hospitals for bedside drug testing, emergency control, in patient treatment control (anticancer therapy) etc. Current research efforts are focused on proteins, tissues, or living cells immobilized in microfabricated configurations for high-throughput drug screening and discovery. Such devices can comprise several different microelectronic sensors and biosensors sensitive, for example, to pH, temperature, impedance, dissolved oxygen, etc. for a multiparametric monitoring. Of equal new interest are the oligonucleotide-immobilized biosensors for interactions studies between a surface linked DNA and the target drug or for hybridisation studies. This short review summarizes several recent trends dedicated to the development and application of biosensors in the pharmaceutical arena. Copyright © Taylor & Francis, Inc.

2004

Preparation, characterization, and application of an enzyme-immobilized magnetic microreactor for flow injection analysis

Enzyme-immobilized magnetic microparticles (EMMP) have been prepared for use as a microreactor in flow injection analysis (FI). The microparticles were directly injected into the FI system. Their retention occurred within the flow line by small permanent magnets located near the detector. The analytical utility of this concept was illustrated by the assay of glucose using glucose oxidase (GOx), immobilized microparticles, and amperometric detection of liberated hydrogen peroxide. The microparticles were derived from silica gel (nominal pore diameter, 15-80 nm) by impregnation with a citric acid/ethanol solution and a ferric nitrate/ethanol solution and then by calcination in a nitrogen atmosphere to produce ferrimagnetic fine particles of spinel-type iron oxide (gamma-Fe(2)O(3)) inside the pore. They were characterized by X-ray diffraction. The calibration curve of the glucose sample (2 microL injected) was linear between 2.5 x 10(-6) and 5 x 10(-4) mol/L (R = 0.9995), and the detection limit was 1.0 x 10(-6) mol/L or 0.36 ng of injected glucose (S/N = 3). The repeatability for a 5 x 10(-4) mol/L glucose solution was RSD = 1.5% (n = 6). Application to the assay of glucose in a fermentation broth is illustrated. The GOx MMP were stable and active for more than eight months when kept at 10 degrees C.

Horseradish peroxidase electrode for the analysis of clozapine

2003

Mediated electrocatalysis at the carbon paste electrode: The iron(III)/hydrogen peroxide model

NO analysis: Foreword

Phenothiazine drugs as redox mediators in Horseradish Peroxidase bioelectrocatalysis

Amperometric determination of choline released from rat submandibular gland acinar cells using a choline oxidase biosensor

A choline (CHO) biosensor based on the determination of H(2)O(2) generated at the electrode surface by the enzyme choline oxidase (CHOx) was developed. The biosensor consisted of CHOx retained onto a horseradish peroxidase (HRP) immobilized solid carbon paste electrode (sCPE). The HRPsCPE contained the molecule phenothiazine as redox mediator and CHOx was physically retained on the electrode surface using a dialysis membrane. Several parameters have been studied such as, mediator amount, influence of applied potential, etc. The CHO measurements were performed in 0.1 M phosphate buffer, pH 7.4. Amperometric detection of CHO was realized at an applied potential of 0.0 mV vs Ag/AgCl. The response is linear over the concentration range 5.0x10(-7)-7.0x10(-5) M, with a detection limit of 1.0x10(-7) M. This biosensor was used to detect choline released from phosphatidylcholine (PC) by phospholipase D (PLD) in isolated rat salivary gland cells stimulated by a purinergic agonist (ATP).

Biosensors

HRP-based biosensor for monitoring rifampicin

Pyrrole was electropolymerized onto a Pt electrode in the presence of LiClO(4) and horseradish peroxidase (HRP). This HRP-based biosensor has been used for the amperometric detection of rifampicin (RIF) in the presence of a constant concentration of H(2)O(2). The C(H(2)O(2)) as well as the applied potential (E(ap)) and the pH of the phosphate buffer have simultaneously been optimized through a central composite design. Under these conditions, repeatability, reproducibility, and stability of the modified electrode have been analyzed. The detection limit for RIF has been calculated taking into account the probability of false-positive (alpha) and -negative (beta), reaching a value of 5.06x10(-6) mol dm(-3). The biosensor was applied to the determination of RIF in pharmaceutical preparations and biological samples.

2002

Biosensor para la determinación de glucosa provisto de una membrana de poliacrilamida con glucosa oxidasa

Potentiometric sensor for hydroxyzine determination

A new polymeric membrane electrode has been developed for the determination of hydroxyzine. The electrode was constructed by solubilizing the hydroxyzine silicotungstate ion pair into a polyvinylchloride matrix plasticized by nitrophenyloctylether. The electrode exhibited a near-Nernstian response (57 mV/decade) in the concentration range comprised between 1 x 10-2 M and 6 × 10-7 with a lower limit of detection of 2.5 × 10-7 M. The electrode response was not sensitive to pH changes between 2.8 and 6.9 and not affected by possible interfering species such as cetirizine and pharmaceutical excipients. The electrode was successfully applied to the determination of hydroxyzine in pharmaceuticals and in a dissolution profile study of tablets. The results were validated by comparison with LC and spectrophotometric assays according to the USP Pharmacopoeia methods.

Fluorimetric determination of alkaline phosphatase in solid and fluid dairy products

A new assay has been developed for measuring residual alkaline phosphatase (ALP) activity in a wide variety of dairy products. The method proposed is simple, rapid and directly applicable to solid and liquid dairy samples. ALP in the test sample hydrolyzes a non fluorescent substrate, trifluoromethyl-beta-umbelliferone phosphate, to its highly fluorescent phenolate product. The assay is performed in a reverse micellar medium composed of mixed buffer (2-amino-2-methyl-1-propanol buffer pH 9.0 and borate buffer pH 9.0) in AOT/isooctane, at a temperature of 38 degrees C. Total test time is 450 s. Reaction rates are linear (except for butter) up to 8.5 and 11% (v/v) raw milk, for whole milk and chocolate milk, respectively. The detection limits are 0.04, 0.4 and 0.22% (v/v) raw milk, for whole milk, chocolate milk and butter, respectively. The precision of the fluorimetric method was assessed by repeated analysis of a pasteurized milk sample spiked with mixed herd raw milk. The accuracy of the method was evaluated by comparison with an official colorimetric assay using p-nitrophenylphosphate as ALP substrate.

Biosensors in the pharmaceutical and biomedical sciences

Les biocapteurs dans le domaine pharmaceutique

Biosensors are analytical devices which incorporate a biological component (enzyme, antibody, animal or plant cell, DNA fragments, lipids.) intimately connected to a physical transducer (electrode, optical fibre, vibrating quartz.). This dual configuration allows the study of a great variety of compounds of pharmaceutical interest which react with the biocomponent. The latter is selected depending on the application and the performance criteria requested. Biosensors are suitable for real time monitoring such as in bioreactors, and for the determination of various physiological and pharmacological parameters. Biosensors may be employed in home testing (glucose, lactate.), in hospitals (bedside testing, emergency, surgery, dialysis monitoring, etc.) in clinical laboratory analyses (immunoassays, DNA analysis.) and at research centres. Ideally, a biosensor should be easy to use, allowing direct analysis without sample pre-treatment. Measurements should be automatized and remote controlled. The biosensor may be miniaturized for single use or for implementation in sensor arrays. Applications to microenvironments (in vivo, single cell.) or discrete one shot decentralized tests may also considered.

Hydrogen peroxide sensitive amperometric biosensor based on horseradish peroxidase entrapped in a polypyrrole electrode

The enzyme horseradish peroxidase (HRP) has been entrapped in situ by electropolymerization of pyrrole onto a platinum electrode. The latter was previously coated by a polypyrrole layer for better adhesion of the biocatalyst film and in order to avoid the enzyme folding onto the Pt electrode. The biosensor allowed the determination of hydrogen peroxide in the concentration range comprised between 4.9 x 10(-7) and 6.3 x 10(-4) M. The biosensor retained more than 90% of its original activity after 35 days of use.

Quality manuscript in analytical chemistry

2001

Electrooxydation potential as a tool in the early screening for new safer clozapine-like analogues

The chemical modification of clozapine (1) has permitted the finding of new analogues, e.g., olanzapine (2), quetiapine (3), 5-(4-methylpiperazin-1-yl)-8-chloropyrido[2,3-b][1,5]benzoxazepine fumarate (9), with a clinical or psychopharmacological profile similar to that of clozapine. However, when developing new derivatives, the designers are discouraged by the development of clozapine-induced agranulocytosis. Different researchers have raised the role played by the oxidizability of the molecule in such a deleterious effect. In the present paper, we examined the oxidation profile (direct scavenging abilities, efficacy in inhibiting lipid peroxidation, and electrooxidation potential) of newly developed methoxy and trifluoromethylsulfonyloxy analogues related to clozapine, some of them being described as putative antipsychotic. The oxazepine derivative 7, unlike the other diazepine derivatives (6, 10--12), was not readily oxidized. Using a statistical predictive model for hematotoxicity previously described, 7 was found in the cluster of potentially nontoxic compounds while diazepine derivatives 6 and 10-12 were classified as potentially toxic compounds. Among these original compounds, 7, which presents a preclinical clozapine-like profile and a low sensitivity to oxidation, could be a promising antipsychotic candidate with low side effects. Considering the tricyclic derivatives examined so far, some elements of structure-oxidation relationship (SOR) might be pointed out. Regarding the nature of the tricyclic ring substituent, from the most to the least sensitive to oxidation, the sequence was as follows: HO > Cl > CH(3)O > CF(3)SO(2)O. The nature of the tricyclic ring influenced also the sensitivity to oxidation; the diazepine moiety appeared to be the most reactive ring compared to oxa- and thiazepine congeners. These parameters could be advantageously integrated in the early design of new safer clozapine-like analogues.

2000

Development of an on-line electrochemical biosensor for glucose determination in rat brain using microdialysis sampling

Reagentless enzyme electrode based on phenothiazine mediation of horseradish peroxidase for subnanomolar hydrogen peroxide determination

The development and characterization of a highly sensitive enzyme immobilized carbon based electrode for the determination of subnanomolar concentrations of hydrogen peroxide in aqueous samples is described. The biosensor consists of horseradish peroxidase (HRP) immobilized in solid carbon paste along with a suitable redox mediator. The latter allows the acceleration of the electroreduction of HRP in the presence of hydrogen peroxide. Several phenothiazines as mediators are investigated in a comparative manner and with respect to dimethylferrocene using cyclic voltammetry and amperometry. Insolubilization of the HRP in the solid carbon paste is achieved by cross-linking the enzyme with glutaraldehyde and bovine serum albumin. Several experimental parameters such as pH, mediator and enzyme content are considered. The hydrogen peroxide determination is better carried out in 0.1 M acetate buffer, pH 4.5, by amperometry at an applied potential of 0.0 V versus Ag/AgCl, 3 M NaCl concentration and by using the phenothiazine base as redox mediator. The biosensor response is linear over the concentration range 2 nM-10 microM with a detection limit of 1 nM. The linear range of the hydrogen peroxide response without a mediator in the biosensor is found between 2 and 40 microM. The biosensor can be used for more than 180 measurements. Additional modification of the electrode by incorporation of Nafion SAC-13 microparticles in the solid carbon paste allows detection of concentrations of hydrogen peroxide as low as 0.1 nM.

Trends in electrochemical biosensors

Oxidation and peroxidation of phenols at carbon paste and peroxidase

1999

Electroanalytical behaviour of a nanoarray self-assembled thiocholesterol gold electrode

Oxidation sensitivity may be a useful tool for the detection of the hematotoxic potential of newly developed molecules

Some antipsychotic agents have been found to produce agranulocytosis and aplastic anemia. The oxidation phenomena and/or the formation of free radicals has been suggested to be causally related to various hematological disorders, e.g., agranulocytosis. Using five experimental conditions, we tested the oxidative potential of compounds with and without a history of hematological side effects, e.g., agranulocytosis and aplastic anemia. A statistical analysis was undertaken for each experimental condition and a multivariate analysis combining all results was performed. Two peroxidase-induced free radical models did not successfully discriminate between drugs with and without a history of causing hematologic problems (<70%). The lipid peroxidation system provided even less satisfactory discrimination, with only 56.25% correct classification. However, an 87.5% correct classification was obtained when using the oxidation potentials of these drugs determined at pH 4.7 and at pH 7.4. A multivariate analysis taking into account the five variables provided 87.5% success in classification. The two clusters were better discriminated in terms of a "distance coefficient." In a second analysis, the putative antipsychotic pyridobenzodiazepine analogues (JL5, JL8, JL18, and JL25) were classified in the cluster of toxic compounds, while the oxa- and thiazepine analogues (JL2, JL3, and JL13) were classified as nontoxic compounds. On the other hand, a few metabolites of clozapine and fluperlapine were classified in the toxic compound group. The procedure described herein is, to our knowledge, the first which classifies molecules of different structures as well as different pharmacological profiles according to their hematotoxic potential. Such a procedure could be used to predict drug-induced hematological side effects.

1998

Electrochemical study of some 2-mercapto-5-R-ammino-1,3,4-thiadiazole derivatives using carbon paste electrodes

The electrochemical study of some 2-mercapto-5-R-ammino-1,3,4-thiadiazole derivatives was made by cyclic and linear sweep voltammetry using a carbon paste electrode (CPE, graphite/solid paraffin ratio 2:1) as working electrode and an Ag/AgCl reference electrode. The current-potential curves were recorded in anodic polarisation in -0.1 and +1.3 V range using aqueous solutions and different buffers (between pH 1.2 and 10.0), with 20 or 50 mV s-1 sweep rate. The oxidation peak appears between +0.65 and +0.70 V due to disulphides formation. The 5-phenyl derivative has two oxidation peaks, the first at +0.45±0.03 V and the second at +0.65±0.03 V. The oxidation potentials are pH dependent, decreasing from 0.9±0.1V at pH 1.2 to 0.6±0.1 V at a pH between 8.0 and 10.0. In some potential ranges depending on pK(a) of molecules the oxidation potential and oxidation current are pH independent. Simple, precise and accurate voltammetric methods for the determination of these compounds were developed and validated in 2.5x10-6-7.5x10-4 mol l-1 concentration ranges. The detection limits were 2.3 μmol l-1 for 5-ammino-, 12.3 μmol l-1 for 5-acetylammino-, 11.6 μmol l-1 for 5-allylammino-, and 1.2 μmol l-1 for 5-phenylammino-2-mercapto-1,3,4 thiadiazole derivatives. Copyright (C) 1998 Elsevier Science B.V.

Critical Comparison of Paraffin Carbon Paste and Graphite-Poly(tetrafluorethylene) Composite Electrodes Concerning the Electroanalytical Behavior of Various Antioxidants of Different Hydrophobicity

Horseradish peroxidase immobilized electrode for drug analysis

Direct fluorimetric determination of theofylline in serum by inhibition of alkalyne phosphatase (AP) activity in reversed micelles

Gold based sensors in pharmaceutical analysis

Comparative study of an on-line system and an implantable modified platinum electrode for continuous monitoring of H2O2 in vivo

Determination of some antibiotic macrolides using voltammetric techniques

The electrochemical study of some 2-mercapto-5-R-amino-1,3,4-thiadiazole derivatives using carbon paste electrodes

Application of a new PVC-based ion-selective electrode for surfactant detection in microflow systems

Horseradish peroxidase immobilized electrode for phenothiazine analysis

1997

Preparation and characterization of bis(8-quinolinato)tin(II)

Alkoxylated p-phenylenevinylene oligomers:

Twenty-one n-alkoxy substituted phenylenevinylene oligomers were synthesized, varying in size, number and position of the OR groups. IR,MS and solubility data are presented. NMR measurements provided the molecular structure as well as information about conformations and molecular dynamics. UV and of cyclic voltammetric data give correlations of chemical structure (number and position of OR substituents) with separate HOMO and LUMO energies.

JL 13, a potential successor to clozapine, is less sensitive to oxidative phenomena

The oxidation behaviour of JL 13, a promising antipsychotic, was investigated in comparison with clozapine and loxapine, by measuring their direct "radical scavenging" abilities and their efficacies in inhibiting the lipid peroxidation. In the lipid peroxidation system, the reactivity of these compounds with free radicals produced by gamma-irradiation of linoleic acid may be presented as follows: JL 13 = loxapine < clozapine. In two enzymatic systems (HRP/GSH and HRP/H2O2/ GSH) which generate the thiyl free radicals, clozapine produces a strong enhancement of the thiyl-radical EPR signal intensity while JL 13 and loxapine exhibit no or minimal effect on this signal. The redox potential values for the three derivatives confirm the spectro-photometric and EPR results. Following this study, we show that JL 13, although presenting a preclinical clozapine-like profile, appears less sensitive to oxidation than clozapine.

Differential pulse voltammetric determination of fenobucarb at the glassy carbon electrode, after its alkaline hydrolysis to a phenolic product

Preparation and characterization of mixed monolayer assemblies composed of thiol analogues of cholesterol and fatty acid

On-line in vivo monitoring of endogenous quinones using microdialysis coupled with electrochemical detection

Self-assembled monolayer gold electrode for surfactant analysis

Electrochemical characterisation of mixed monolayer assemblies of thiol analogues of cholesterol and fatty acids on gold

A self-assembled monolayer (SAM) on gold prepared from a binary mixture of a thiol analogue of cholesterol (thiocholesterol, TC) and a functionalised alkanethiol (11-mercaptoundecanoic acid, MUA) has been investigated by voltammetry. The voltammetric results are in agreement with previously reported spectroscopic data and show that the geometric arrangement and composition of the molecules in the mixed monolayer controls the heterogeneous electron transfer process of Fe(CN)3-6 across the assembly. The quantitative description of the influence of TC on the electron transfer rate constant is given through Tafel plots. At the pure MUA SAM electrode, the electron transfer is governed by penetration through the monolayer. The introduction of TC into the SAMs creates defects giving rise to diffusion controlled electron transfer in addition to penetration. By raising the TC content the electron transfer rate constant increases due to diffusion. This behaviour can be explained by a model in which the assembly goes from a penetrative but defect-free film barrier (pure MUA SAM) via a structure with defects in the mixed composition regime to a defect-rich structure consisting of an array of ultramicroelectrodes (pure TC SAM). © 1997 Elsevier Science S.A.

Electrochemical behavior of H2O2 on gold

Potentiometric analysis of surfactants

1996

Electrode enzymatique pour l'analyse des phénols et catéchols d'intérêt pharmaceutique

Electrochemical Oxidation of 8-Hydroxyquinoline and Selective Determination of Tin(II) at Solid Electrodes

Thiocholesterol on gold

The formation of thiocholesterol (TC) monolayers on gold has been studied by ellipsometry, contact angle measurements, infrared spectroscopy, and cyclic voltammetry. Subsequent treatment of the TC assembly with 11-mercaptodeuterioundecanoic acid (MDUA) shows that the average surface coverage is about 65% of that of a self-assembled alkanethiolate monolayer and that it has a large number of molecular defects. These defects exist because of a mismatch between the size and shape of the TC molecule and the pinning distance at the Au(111) crystal lattice. Potential uses of these defect-rich structures are microelectrode arrays for electroanalytical and biosensor applications.

Electrochemical analysis of surfactants:

This work presents an overview of electrochemical techniques, namely potentiometry, amperometry, tensammetry, electrocapillary measurements and biosensors, recently applied for the determination of surfactants.

A damping system for syringe pumps used for microdialysis with on-line electrochemical detection

Electrochemical oxidation of oxine and selective determination of tin (II) at solid electrodes

The potential of electroanalytical techniques in pharmaceutical analysis

With the considerable progresses observed in analytical instrumentation, it was of interest to survey recent trends in the field of electroanalysis of drugs. Potentiometric, voltammetric and amperometric techniques were scrutinized both in terms of historical evolution and in terms of potentialities with respect to the analysis of drugs in various matrices. With regard to the former, it appeared that numerous original selective electrodes (for drugs and ions) have been studied and several ion-selective electrodes have been successfully commercialized. Improvements are still expected in this field in order to find more robust membrane matrices and to minimize the surface fouling. Electrochemistry is well suited for trace metal analysis. A renewed interest in potentiometric stripping analysis is observed and is stimulated by the power of computers and microprocessors which allow rapid signal recording and data handling. Polarography and its refinements (Pulsed Waveform, Automation,...) is ideally applied for trace metal analysis and speciation. The technique is still useful in the analysis of drug formulations and in biological samples provided that the method is adequately validated (selectivity!). The same holds for solid electrodes which are currently routinely applied as sensitive detectors after chromatographic separation. New instrumentation is soon expected as regard electrochemical detection in capillary electrophoresis. Actually, in order to increase the responses and improve the selectivity, solid electrodes are facing exponential research dedicated to surface modifications. Perm-selectivity, chelations catalysis, etc. may be considered as appropriate strategies. Microelectrodes and screen printed (disposable) sensors are of considerable interest in cell culture e.g. for single cell excretion analysis and in field (decentralized) assays, respectively. Finally several biosensors and electrochemical immunoassays have been successfully development for the selective and sensitive analysis of drugs.

Determination of tin(II) in pharmaceuticals by amperometric oxidation after complexation with tropolone

Study of a new solid carbon paste tyrosinase-modified amperometric biosensor for the determination of catecholamines by high-performance liquid chromatography

The performance of a tyrosinase-modified 'solid carbon paste' electrode (SCPE) as electrochemical detector has been studied in comparison with a glassy carbon electrode detector in high-performance liquid chromatography for the simultaneous determination of dopamine, 3,4-dihydroxyphenylacetic acid, norepinephrine and homovanillic acid. The influence of pH, flow-rate and amount of organic solvent in the mobile phase on the biosensor response was investigated. The stability and selectivity of the detector were significantly affected by the mobile phase pH. No effect of 2% isopropanol in the mobile phase was observed. The biosensor response was fast, reproducible, highly sensitive and linear over the concentration range 0.09 μM-1 mM (detection limit of ca. 290 pg of neurotransmitter injected).

On the origin of the differences between stearic-acid-modified carbon paste electrode performances after exposure to surfactant and brain tissues

Stearic-acid-modified carbon paste electrodes (StCPEs) were investigated by cyclic voltammetry and chronoamperometry, as a function of paste composition, before and after treatment by surfactant and brain tissues. It was found that the amount and viscosity of the carbon paste binding agent were important parameters, which may explain the differences in the literature data on ascorbic acid (AA) and dopamine (DA) resolution at StCPEs. The ionic strength of the investigated media was also shown to affect the voltammetric discrimination between AA and DA. The use of solid paraffin for StCPE preparation was shown to offer significant advantages in terms of robustness and voltammetric performance.

1995

Cyanide determination using an amperometric biosensor based on cytochrome oxidase inhibition

Inorganic tin(II) determination by FIA with amperometric detection of its oxinate complex

A highly selective, rapid and direct amperometric method, based on the formation of a complex between tin(II) and 8-hydroxyquinoline (oxine), has been developed for the determination of trace levels of tin(II) using flow injection analysis. Tin(II) electro-oxidation was catalyzed by oxine; its oxidation peak occurred at +0.05 V vs. Ag/AgCl at a glassy carbon electrode in 0.1 mol 1(-1) acetate buffer (pH 6). A linear relationship was obtained between the peak current and the tin(II) concentration in the range 0.25-20 mumol 1(-1). The detection limit was 0.1 mumol 1(-1) and the relative standard deviation calculated by the injection of a 10 mumol 1(-1) tin(II) solution was 5% (n = 20). Optimization of several experimental parameters has been carried out and the influence of numerous cations and possible interfering molecules encountered in radiopharmaceuticals and in dental gels has been investigated. The method was applied to the determination of tin(II) in dental gels.

Preparation and characterization of a new electrode based on solid paraffin and immobilized tyronase

New carbon paste electrode for development of biosensors

Sensors based on carbon paste in electrochemical analysis

Cephalosporin antibiotics at carbon paste and modified carbon paste electrodes in both aqueous and biological media

A sensitive voltammetric method has been developed for the oxidation and determination of the cephalosporin antibiotics Cefatrexyl, Velosef, Claforan, Cefobid and Rocephin at both carbon paste and modified fatty acid carbon paste electrodes. The electroanalytical technique used was direct current stripping voltammetry. The adsorptive stripping response was evaluated as a function of preconcentration time, preconcentration potential, modifier percentage and other variables. The effect of the interfering materials such as ascorbic acid, uric acid and some metal ions, i.e. Cu(II) and Fe(III), has also been taken into consideration. A detection limit down to 10-8 M has easily been achieved. Application of the method to biological samples (e.g. urine and serum) has been assessed. © 1995.

Analytical application of self assembled monolayers on gold electrodes

Polycrystalline bare gold electrodes have been used as substrate for the preparation of self assembled monolayers (SAMs) of alkanethiols. Chemical cleaning and several mechanical polishing procedures of the electrode have been carefully tested in order to prepare monolayers of octadecyl-, mercaptans. By analyzing the cyclic voltammetric curves of hexacyanoferrate III and chlorpromazine and the electrochemical desorption of the coated monolayer, it appeared that the response at the bare electrodes is related to the cleaning procedure and that the structure of SAM coated gold electrodes is influenced by the polishing material used, i.e. diamond or alumina slurry. Electrochemical results have been confirmed by Auger analysis of the electrode surface. © 1995.

Sensors based on carbon paste in electrochemical analysis: A review with particular emphasis on the period 1990-1993

A review is presented dealing with the use of carbon paste as an electrode maaterial for electrochemical sensors (311 references). It covers mainly publications which appeared during the period 1990-1993; numerous applications demonstrate the widespread applicability of carbon paste in the field of electrochemical analysis, such as voltammetry, amperometry, and potentiometry, but also as an electrode for electrochemical detectors in flow systems. Copyright © 1995 VCH Verlagsgesellschaft mbH

1994

Preparation and Characterization of Octadecylamine-Containing Carbon Paste Electrodes

Surfactant modified carbon paste electrode

The hexadecylsulfonic acid (sodium salt) modified carbon paste electrode (HDSNa‐CPE) has been studied in batch and flowing systems, and its analytical performance has been established in comparison with a conventional carbon paste electrode (CPE). Amperometry, linear scan, and preconcentration voltammetry have been used for the investigation of several analytes of pharmacological interest. Because of the presence of surface functionalities, markedly different electrode responses have been observed at the HDSNa‐CPE depending on the nature (hydrophobicity and charge) of the investigated molecule. The HDSNa‐CPE showed, in linear scan voltammetry and for all the species investigated, higher responses compared to the CPE. The HDSNa‐CPE showed important current enhancements in voltammetric analysis of hydrophobic organic cations in acidic media and at low ionic strength. Copyright © 1994 VCH Publishers, Inc.

Amperometric biosensor based on carbon paste mixed with enzyme, lipid and cytochrome c

Surfactant modified carbon paste electrode

The modification of the carbon paste electrode (CPE) with the amphiphile hexadecyl sulfonic acid (sodium salt) has permitted the development of a stable and analytically useful functionalized electrode. The electrochemical characterization of the modified electrode (potential range, background current, stability) has been investigated by cyclic voltammetry in aqueous media with different buffer compositions and in hydro‐organic media and the results compared favorably with the conventional carbon paste electrode. The characterization of the sulfonated functionalities and their influence in the electrode behavior has been pointed out using linear scan and adsorptive voltammetry by studying two model compounds: promethazine and ascorbic acid. The marked influence of the pH, ionic strength, and nature of the buffer cation on the shape (potential and intensity) of the voltammetric curves confirmed the structure of the modified electrode interface, i.e., electrode bearing strong cation exchange functionalities. Scanning electron microscopy and optical microscopic observations of the CPE and modified CPE showed a higher density of graphite particles not covered by liquid paraffin at the latter. Copyright © 1994 VCH Publishers, Inc.

Trends in electroanalytical research and instrumentation

Quantitative analysis of zopiclone in tablets using ion‐selective electrode and polarographic methods

Different types of PVC‐matrix ion‐selective electrodes (ISEs) that respond to the cationic form of zopiclone are described. Four ion‐pairing agents, namely tetraphenylborate (TPB), reineckate (RN), phosphotungstate (PT) and silicotungstate (ST), and different plasticizers are investigated. The best PVC polymeric membrane contains nitrophenyloctylether (NPOE) as plasticizer and zopiclone‐TPB as active material. This electrode exhibits a Nernstian response (60 mV per decade) in the range 1 × 10−2 to 1 × 10−5 M and a fast dynamic response time, this response being not affected by pH between 1.9 and 5.5. Direct potentiometry was used to determine zopiclone in drug formulations using this new zopiclone‐selective electode. The results are comparable to those obtained by differential pulse (DP) and square‐wave (SW) polarographic techniques using both direct and standard addition methods. Copyright © 1994 VCH Verlagsgesellschaft mbH

1993

Characterization of mediated and non-mediated oxidase enzyme based glassy carbon electrodes

Investigation of the batch injection analysis technique with amperometric biocatalytic electrodes using a modified small-volume cell

The performance of the recently developed batch injection analysis (BIA) technique was investigated with regard to the behaviour of enzyme-immobilized electrodes. Glucose oxidase and xanthine oxidase sensors were prepared by casting the enzyme-immobilized membranes on the electrode surface. The measurements are based on the amperometric detection of the product of the enzymatic reaction: hydrogen peroxide at + 650 mV vs. Ag/AfCl (GOx) or the reduced form of methylene blue at + 50 mV vs. Ag/AgCl (XOD). The enzyme glutamate dehydrogenase was incorporated in the carbon paste and the direct and phenaxine methosulphate-mediated detection of NADH was followed at the enzyme electrode. The major characteristics observed were simplicity of the equipment, a high sampling rate and limited consumption of the carrier, i.e., reagents such as the mediator and cofactor. The repeatability of the manual injection of the sample was shown to be the critical step in the BIA mode. A new BIA cell design, allowing semi-continuous solution draining, is reported.

Characterization of mixed enzyme mediator carbon paste electrodes

Amperometric bioelectrodes based on carbon paste mixed with glucose oxidase (GOX) and dimethylferrocene (DMFc), are characterized by using cyclic voltammetry, potential step chronoamperometry and amperometry at a rotating disk electrode. The catalytic process appears to be highly dependent on the amount of DMFc. Kinetic control, internal diffusion control and external diffusion control can be obtained only by varying the amount of incorporated DMFc. It was shown that the Eadie-Hofstee plot is a particularly useful tool in diagnosis of diffusional limitations. The high efficiency of electrochemical regeneration of high amounts of DMFc∗ surrounding GOX solves the problem of co-substrate transport. The catalytic oxidation current of ascorbic acid was highly diminished by casting a lipid/Nafion membrane and totally eliminated by treatment of the sample with hydrogen peroxide prior to measurement. © 1993, Taylor & Francis Group, LLC. All rights reserved.

Electrochemical determination of iron in YBa2(Cu1-xFex)3O7 superconducting compounds

Pharmaceutical and biomedical applications of electroanalysis :

Various aspects of the application of electrochemical techniques in drug analysis are scrutinized. Considerations regarding the adequacy of modern polarographic and voltammetric methods for the determination of drugs in various samples are discussed. A tentative validation scheme for electroanalytical methods is illustrated.

Electrochemical determination of iron in YBa2(Cu1-xFex)3O7 superconducting compounds

The electrochemical determination of iron in doped YBaCuO superconducting compounds has been investigated by differential pulse polarography (SMDE) and by differential pulse voltammetry using a glassy carbon electrode. A well‐defined peak for iron was observed at -0.15 V (vs. Ag‐AgCl) reference electrode in sodium citrate/EDTANa2H2 pH 6. The electrochemical results have been validated by spectroscopic procedures, including atomic absorption and energy dispersion X‐ray spectroscopy. The differential pulse polarography using the standard addition method for peak validation has been found to be most appropriate. Copyright © 1993 VCH Publishers, Inc.

1992

Enzyme electrode biosensors: theory and applications.

Preparation and characterization of a fragile enzyme immobilized carbon paste electrode

Determination of cisplatin in human plasma by HPLC with a glassy carbon based wall jet amperometric detector

Electrochemical behaviour of tizanidine at solid electrodes

The electrochemical behaviour of tizanidine [5-chloro(delta-2-imidazolinyl-2-amino)-4-benzothiadiazole-2,1,3], a centrally-active skeletal muscle relaxant has been investigated in aqueous media at the carbon paste electrode (CPE). Cyclic voltammetry at different pH values, controlled potential coulometry and comparative studies on three structurally related molecules have permitted identification of the oxidation site of tizanidine and suggest possible oxidation products in acidic media. The electrochemical reduction at the CPE occurred in one irreversible step and the reduction product (diamine derivative) was detected and characterized on the positive going scan in cyclic voltammetry. Quantitative measurements of tizanidine within the range 2 x 10(-5) M and 1 x 10(-4) M have been realized at the CPE using the differential pulse technique.

1991

Determination of cis platin in biological fluids and plasma samples by HPLC and oxidative electrochemical detection

Amperometric biosensors for glucose based on carbon paste modified electrodes

Spectrophotometric and electroanalytical study of minoxidil

Polarographic reduction of minoxidil (lxl0-5 - 5x10-4 M) and spectrophotometric study were carried out at different pH;s pK values of the acid-base equilibria were calculated using both techniques. In addition, detection limits and sensitivity were determined using electrochemical (tast, differential pulse and pseudoderivative pulse polarography) and spectrophotometric techniques. A simple method is described for the determination of this compound in pharmaceutical formulations. Electrochemical oxidation was also performed at carbon paste and at lipid modified carbon paste electrodes. © 1991, Taylor & Francis Group, LLC. All rights reserved.

Long-term operational stability of a mixed glucose oxidase-redox mediator-carbon paste electrode

The amperometric response of a mixed-glucose oxidase-redox mediator-carbon paste electrode, permanently poised at the operating potential, has been investigated in phosphate buffer as a function of glucose concentration over a period of four weeks. © 1991, Taylor and Francis Group, LLC. All rights reserved.

1990

Convection/diffusion- and diffusion-controlled rapid-scan voltammetry in HPLC systems with a large-volume wall-jet detector

On-line voltammetric measurements under liquid chromatographic (LC) conditions yield voltammograms which are either purely diffusion- or purely convection/diffusion-controlled, or a combination of both. The dependence of this behaviour on flow-rate, scan-rate and electrode diameter is investigated for a large-volume wall-jet detector. It is shown that for 4 V s-1 scan-rates at 1 ml min-1 flow-rates (conventional LC conditions), S-shaped (convection/diffusion-controlled) voltammograms can be obtained with macro-electrodes (≥ 1 mm diameter). Distortion of voltammogram shape by the cell time constant is discussed for macro-electrodes. The behaviour of the cell in microbore and micro-LC applications is demonstrated. The advantage of being able to change from convection/diffusion-controlled to diffusion-controlled behaviour is discussed.

Electrochemical behaviour of marcellomycin at lipid modified carbon paste electrodes

A lipid-modified carbon-paste electrode is prepared by mixing phospholipids with the carbon-paste matrix. The resulting electrodes have polar head-groups which allow interactions with positively charged drugs and improved preconcentration/extraction steps. The accumulation of the antitumor drug, marcellomycin, is enhanced in the presence of lipids, giving an 8-fold enhancement of current. The electrode response has been optimized with respect to paste composition, nature of the lipid, pH, temperature, and stirring time. A mechanism for marcellomycin accumulation is proposed, based on electrochemical and UV-visible spectrometric measurements as a function of pH. The electrode response is linearly related to the marcellomycin concentration within the range 1 x 10(-8)-6 x 10(-6)M. Known amounts of marcellomycin added to a urine sample diluted sixfold with water have been measured by use of the medium-exchange technique.

Voltammetric determination of Celiptium with carbon paste and lipid-modified carbon paste electrodes

The electrooxidation of the antitumour drug 2-methyl-9-hydroxyellipticinium (Celiptium) was investigated by cyclic, differential-pulse and adsorptive voltammetry at carbon paste (CPE) and lipid-modified carbon paste electrodes (LM-CPE). The influence of the paste composition, i.e., the ratio of graphite to binder, was studied in order to elucidate the nature of the accumulation process at the surface of the CPE. The electrode surface coverage at saturation was calculated. A.c. measurements at the CPE and at the LM-CPE during the accumulation of Celiptium demonstrated an increased differential double layer capacity of the LM-CPE. The influence of several parameters that affect the adsorptive step at the CPE was investigated, such as pH, ionic strength and interfering ions. Improved signals were obtained at the CPE and the detection limit in 0.1 M sodium perchlorate (tacc.=3 min) was found to be 2 × 10-10 M. Measurements of the drug in dilute standard serum samples were done using the medium-exchange technique. © 1990.

Electrochemical behaviour of drugs at lipid modified carbon paste electrodes

Mixing carbon paste with a charged lipid, in an appropriate ratio, permitted us to prepare a modified electrode whose surface exhibits interesting characteristics of the constituting lipid. Two negatively charged phospholipids have been selected, namely: asolectin and cardiolipin. By investigating the electrooxidation of several drugs which are known to interact strongly with the lipid component of cellular membranes (adriamycin, epirubicin and promethazine) it was possible to demonstrate markedly different behaviour at the lipid modified carbon paste electrode (LMPCE) depending on the pH of the solution. By analysing the results of linear scan, ac and adsorptive voltammetry and by taking into account literature data on drug-membrane interactions, it was possible to postulate a model of the LMCPE interface with thin layers of lipids covering the graphic particles. The differential capacity measurements as a function of time (fixed potential) and in the presence of increasing amounts of drugs enabled us to point out profound increases in the capacity of the LMPCE in the presence of adriamycin and epirubicin. In addition, the more negatively charged the lipids were, the higher was the capacity increase.

Electrochemical behaviour of pharmacologically interesting seleno-organic compounds.

1989

Hydrophobic stripping voltammetry using a lipid-modified glassy carbon electrode

Electrochemical behavior of spiroplatin at carbon paste and platinum electrodes

Comportement d'une électrode de carbone vitreux modifiée par dépôt de couches phospholipidiques

Etude de la réduction électrochimique du clotiazepam en milieu aqueux et non-aqueux

Electrochemical behaviour of a lipid modified enzyme electrode

Electrochemical behavior of iproplatin at tha carbon paste electrode

The electrochemical redox behavior of iproplatin (JM9) was investigated at the carbon paste electrode using cyclic voltammetry in the absence and presence of free chloride ions. In the absence of chloride, a diffusion‐controlled, two‐electron reduction peak (Epc1) is observed, giving a platinum(II) derivative that is oxidized to a Pt(IV) compound on cycling (Epa1). Photolytic reduction‐hydrolysis to two platinum(II) derivatives results in a Pt(II) compound which on anodic scanning is oxidized to a Pt(IV) compound (Epa2) that is subsequently reduced to'a Pt(II) compound on cycling, to give rise to a second (earlier) reduction peak (Epc2). The other (nonhydrolyzed) photolytic reduction Pt(II) product can also be reduced (E pc2′) to give Pt(O) that subsequently is oxidized to Pt oxides (E pa*); this latter Pt(II) compound is prevalent in the presence of chloride ions, which inhibit hydrolysis. Copyright © 1989 VCH Publishers, Inc.

Adsorptive stripping voltammetry applied to drug analysis

A brief review of the principles and instrumentation of adsorptive stripping voltammetry is presented and the advantages of the method are described. As for many highly sensitive techniques applied to the analysis of complex media, severe interferences may occur. Different approaches can be used to circumvent these problems, exemplified by several applications in biological fluids. The application of modified electrodes to enhance selectivity is discussed.

Carbon paste electrodes modified by fatty acid applied of drug analysis

Preconcentration and determination of promethazine at lipid modified carbon paste electrodes

Preconcentration and determination of promethazine at lipid‐modified carbon paste electrodes

Lipid‐modified carbon paste electrodes were electrochemically characterized and their potential for drug analysis was compared with conventional carbon paste electrodes. The presence of lipids (phospholipids, fatty acids) in the paste matrix provided enhanced current responses with improved reproducibility. With 5 minutes of accumulation, phenothiazines exhibit a 40‐fold enhancement of the response compared to that obtained without accumulation. As a result, a detection limit of 1 × 10−9 M was attained. The response was characterized with respect to pH, preconcentration potential, accumulation time, paste composition, possible interferences, and other variables. The determination of the tranquilizer in serum and urine required no preliminary treatment other than dilution with phosphate buffer and medium exchange. Detection limits are 5 × 10−8 M in urine and 2 × 10−7 M in serum. Copyright © 1989 VCH Publishers, Inc.

1988

Carbon-polymer chips as sensitive electrochemical detectors for micro-lqiuid chromatography

Redox behaviour of cis-platin at solid electrodes

A comparison of glassy-carbon and carbon-polymer composite electrodes incorporated into electrochemical detection systems for high-performance liquid chromatography

A comparison has been made of the performance of a novel composite carbon-polymer electrode and a glassy-carbon electrode for use as working electrodes in an electrochemical detector for HPLC. The composite electrode was found to be comparable to the glassy-carbon electrode in terms of current response, superior in terms of cost, machinability, noise levels, stabilization time and accessible potential range, and inferior in terms of the potentials required for the oxidation of certain model compounds such as epinephrine and norepinephrine.

Application des stimulations électromagnétiques pulsées (EMFT) sur diverses pathologies de l'appareil locomoteur humain et équin

Enzyme electrodes for the sugar substitute aspartame

A sensor for aspartame (L-aspartyl-L-phenylalanine methyl ester) is prepared by chemical immobilization of L-aspartase on an ammonia-selective electrode. Semi logarithmic response (E vs. log C) was observed in the 1x10-3-1x10-2 M range with a slope of -30 mV/decade. The sensor is stable for more than eight days. The probe is successfully used for the assay of aspartame in commercially available sweeteners.

1987

Enzyme-based electrodes as analytical tools

Redox behaviour of anti-tumor platinum (II) compounds carboplatin at solid electrodes

The electroactivity of a cytostatic complex of platinum (II) possessing no halide ligand (carboplatin) has been studied in aqueous media using platinum and carbon paste electrodes. Cyclic voltammetry has been conducted in order to elucidate the redox behaviour of carboplatin as a function of chloride concentration. Reduction was not observed although oxidation was detected. The nature of the compounds formed during the electro-oxidation was directly related to free chloride ions. At the carbon paste electrode, the reduction of the oxidized species occurred in two steps with the formation of cis-platinum structures and a subsequent electrodeposition of platinum particles. The surface modification step at the carbon paste electrode has demonstrated electrocatalytic properties of the electrode towards platinum (II) complexes possessing halide ligands in their structures. Electrodeposition of platinum ions at a platinum electrode surface as well as a judicious choice of working parameters allows quantitative determinations in the concentration range 3 x 10(-4) - 1 x 10(-5) M.

Polarographic behaviour of trazodone

Voltammetric oxidation of trazodone

Comportement éléctrochimique de la marcellomycine sur électrodes solides

Square wave cathodic stripping voltammetry of marcellomycine:

1986

Electrochemical study of thiols and disulfides using modified electrodes

The electrochemical oxidative behavior of cysteine and several disulfides, such as cystine, lipoic acid and disulfiram, have been investigated using a carbon paste (EPC) and a modified carbon paste (EPCM) electrode. The study has permitted the differentiation of the oxidative behavior of the thiol and of the disulfides. Modification of the carbon paste, by incorporating cobalt(II) phtalocyanine, offers interesting properties due to the electrocatalytic capability of the electrode. Using these types of electrodes the different molecules have been quantitatively determined at concentrations as low as 2.10-7M. © 1986, Taylor & Francis Group, LLC. All rights reserved.

Voltammetric and chromatographic assay of trazodone

Trazodone, a triazolopyridine derivative with antidepressant activity, is irreversibly oxidized in two steps in a large range of scan rates. The first peak shows a linear dependence on trazodone concentration. This behaviour is used for analytical purposes in determining trazodone concentrations in commercial preparations. An original alternative gas-liquid chromatographic method is also developed. Comparison of the chromatographic with voltammetric methods shows that a) both are sensitive enough to be applied to single tablet assays; b) the major advantage of the voltammetric method for analytical purposes lies in the rapid determination of the trazodone content in tablets. Preparation of the samples is easy and no extraction procedure is required. © 1986, Taylor & Francis Group, LLC. All rights reserved.

Oxydation éléctrochimique de la khelline et de l'amikhelline:

Electrodes modifiées à base de phtalocyanine de cobalt

Electrochemical behaviour of benzofuran derivatives of pharmaceutical interest at solid electrodes

1985

Modified electrodes

Composite Materials Used as Modified Electrodes for Pharmaceutical and Clinical Analysis

Caractéristiques électrochimiques d'un nouvel antiinflammatoire non-stéroidien : le piroxicam

Voltammétrie du tryptophane à l'aide d'électrodes solides

Contribution à l'étude analytique du piroxicam

Butyrophenonok elektrokémiai oxidiacioja modositott azén alapu elektrodokon

Unusual electrochemical behaviour of a new phénothiazine

Voltammetry of pharmaceuticals using different types of modified electrodes

Cyclic voltammetry was used to study the electrochemical behaviour of several chemically interesting drugs on different types of carbon based electrodes. The behaviours of the carbon paste and glassy carbon electrodes were investigated and compared with the results obtained with home-made new types of modified electrodes based on colloidal graphite or carbon black dispersed in a suitable polymer. The behaviour of the couple hexacyanoferrate-(II/ III) has been reported as a typical model of depolarizer. It has been shown that electrode responses were markedly influenced by the nature of the substrate. Performances of each electrode have been evaluated with regard to the shape of the voltammetric curves obtained during the investigation of these drugs. © 1985 Springer-Verlag.

Voltammetry of molecules of pharmacological importance at modified electrodes. An analytical and mechanistic point of view

Butirofenonok elektrokémiai oxidációja módosított szén alapú elektródokon

1984

Redox behaviour of pharmaceuticals using voltammetric technique

Bacterial, enzyme and polymeric electrodes applied to drug electrochemical investigations

644 - Tentative correlation between the electrochemical oxidation of neuroleptics and their pharmacological properties

A number of drugs are largely metabolized after oral administration, especially by redox processes. Among the neuroleptics, loxapine, clotiapine and clozapine, which are seven-membered tricyclic molecules with a piperazine side-chain, are known to be extensively metabolized by oxidation. An electrochemical study of these compounds was initiated in order to determine their in vitro redox properties and to elucidate their oxidation mechanisms. The measurements were carried out in aqueous and non-aqueous media using voltammetric, cyclic voltammetric, coulometric, exhaustive electrolysis and thin-layer spectroelectrochemical techniques. The oxidation mechanisms, which differ essentially depending on the pH of the solution, are suggested. In view of these results, various similarities have been detected between the in vitro oxidation processes and the pharmacological behaviour reported in the literature. For example, the importance of the piperazine side-chain has been pointed out: oxidation no longer occurs if this side-chain is protonated; similarly, binding to the receptor is prevented if the lone electron pair of the tertiary atom is occupied. Nucleophilic additions have also been observed in non-aqueous media and the compounds have been identified using classical spectroscopic techniques. If the oxidation mechanism is identical on the piperazine chain for the three compounds, the process is somewhat different when it occurs on the tricyclic ring. Loxapine and clotiapine exhibit different behaviour from clozapine, in their electrochemical as well as in their pharmacological properties.

Study of the electrooxidative behaviour of 5-hydroxyindole-3-acetic acid, 5-hydroxytryptophan and serotonine in the presence of sodium ethylenediaminetetraacetic acid

Ultra-microdetermination of thallium ions and related toxic metals using a new modified electrode

Identification des produits de la réduction électrochimique d'un nouvel anti-inflammatoire : le piroxicam

Nouveau modèle d'électrode enzymatique pour la détermination du glucose : applications aux milieux biologiques

Nouveau modèle d'électrode modifiée à base de carbone et de polymère

Oxydation électrochimique de butyrophénones à l'aide d'électrodes modifiées à base de carbone

Electrodes modifiées

1983

Voltammetric oxidation of pharmaceutical organic compounds at a new modified electrode: The aluminum graphite spray-covered electrode

Détermination de carbamates et d'amides à l'aide d'une électrode à diffusion gazeuse d'ammoniac

Electrochimie de substances médicamenteuses en utilisant de nouveaux modèles d'électrodes modifiées

1982

Etude électrochimique d'un nouveau neuroleptique:

Comportement électrochimique anodique de neuroleptiques en milieu aqueux et non-aqueux

L'électrode à pâte de carbone modifiée.

The various problems which are associated with the use of carbon paste electrode as thin mercury film electrode (TMFE) for anodic stripping voltammetry (ASV) can be overcame in a very easy and rapid way. The procedure consists to coat the carbon paste surface by spraying a graphite based conductive solution. For example, the dispersion of colloidal graphite in a mixture of methyl polymethacrylate with butyl acetate (as solvent) gives interesting results. Such a surface is easily renewable and the electrode does not require any pretreatment procedure like cleaning or polarization cycles., after coating. The technique offers the advantage to limit the risk of sample contamination and memory effects. After pulverisation, a hard, uniform and compact layer is formed after evaporation of the solvent excess. © 1982, Taylor & Francis Group, LLC. All rights reserved.

Preparation and characterization of graphite modified metallic electrodes

Détermination de carbamates et d'amines à l'aide d'une électrode à diffusion gazeuse d'ammoniac

La voltammétrie par redissolution appliquée à la micro-analyse des métaux lourds dans les milieux biologiques et les denrées alimentaires

The graphite spray electrode and its application in the anodic stripping voltammetry of bismuth

Preparation and characterization of graphite-coated metallic electrodes : the graphite-sprayed electrode

1981

A rapid determination of trace amounts of bismuth in urine and blood using differential pulse anodic stripping voltammetry at the hanging mercury electrode

1979

Electrochemical oxidation of derivatives of dibenzodiazepin, dibenzothiazepin and dibenzoxazepin