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Biomedical subjects

J M Kauffmann

Publications and source records attributed to J M Kauffmann.

At least 19 recordsLinked to original sources
PubMed2003

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.

Biosensing Techniques↗
PubMed2003

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).

Adenosine Triphosphate↗
PubMed2002

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.

Biosensing Techniques↗
PubMed2002

[Biosensors in the pharmaceutical domain].

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.

Biosensing Techniques↗
PubMed2001

Electrooxidation 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.

Antioxidants↗
PubMed2000

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.

Biosensing Techniques↗
PubMed1999

Oxidation sensitivity may be a useful tool for the detection of the hematotoxic potential of newly developed molecules: application to antipsychotic drugs.

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.

Agranulocytosis↗
PubMed1998

Fluorimetric determination of theophylline in serum by inhibition of bovine alkaline phosphatase in AOT based water/in oil microemulsion.

Theophylline is an effective bronchodilatator used in the treatment of asthma which requires frequent control because of its narrow therapeutic index. Over the past decade much attention has been dedicated to the peculiar properties of the inner water pools of AOT (sodium 2-bishexyl-ethyl sulfosuccinate) microemulsions as enzyme microreactors, yet few analytical applications of the latter have been reported. We developed an original assay based on the uncompetitive inhibition by theophylline of the reaction catalyzed by alkaline phosphatase from bovine liver (E.C. 3.1.3.1) of the ELF-97 fluorogenic substrate in borate buffer 20 mM (pH 8.6)/AOT/iso-octane-ethyl acetate (95:5) at a temperature of 37 degrees C. Optimal activity of endogenous plasmatic alkaline phosphatase isoenzymes approximately pH 10.5, interfering activity of the serum are avoided. The assay is multiple point rate, monitoring the appearance of the photostable fluorescence emission of the reaction product (510-530 nm) out of the water pool. The influence of several parameters such as the amount of buffer (W(o)), the amount of alkaline phosphatase, sample volume (10-30 microl) [corrected], optimal run time (1-7 min) and the use of phosphorylating acceptor (2A2MP) are discussed. The method was compared to HPLC UV and TDx methods.

Alkaline Phosphatase↗
PubMed1998

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 +/- 0.1 V 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 pKa 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 2.5 x 10(-6)-7.5 x 10(-4) mol l(-1) concentration ranges. The detection limits were 2.3 micromol l(-1) for 5-ammino-, 12.3 micromol l(-1) for 5-acetylammino-, 11.6 micromol l(-1) for 5-allylammino-, and 1.2 micromol l(-1) for 5-phenylammino-2-mercapto-1,3,4 thiadiazole derivatives.

Electrochemistry↗
PubMed1997

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.

Antipsychotic Agents↗
PubMed1996

Fluorimetric determination of tin and organotin compounds in hydroorganic and micellar media in the presence of 8-hydroxyquinoline-5-sulfonic acid.

The fluorescence of tin(IV) complexed by 8-hydroxyquinoline-5-sulfonic acid (8-HQSA) has been studied in both aqueous and hydroorganic (acetate buffer and dimethylsulfoxide) media. Several experimental parameters such as pH, DMSO/water ratio and reactant concentration have been investigated to increase the fluorescence of the tin(IV)-8-HQSA complex. A linear relationship between tin(IV) concentration and fluorescence intensity was observed between 1.7 and 20 microM). Mechanistic and quantitative studies in the presence of surfactants have been performed. Judiciously selected micellar media permitted solubilisation and quantitation of tin(IV) as well as dibutyltin compounds. A linear relationship between concentration and fluorescence intensity was found for mono-, di- and tributyltin with detection limits of 0.1 microM, 0.7 microM and 1 microM, respectively.

Dentifrices↗
PubMed1996

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.

Automation↗
PubMed1989

Adsorptive stripping voltammetry applied to drug analysis: a powerful tool.

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.

Adsorption↗
PubMed1989

Applications in drug analysis of carbon paste electrodes modified by fatty acids.

The oxidation of promethazine as a model compound has been studied by adsorptive stripping voltammetry at carbon paste electrodes (CPE). A modification of the carbon paste matrix with fatty acids allows greater preconcentration of the molecule at the electrode surface. Several fatty acids of different chain length have been tested. The modification of the CPE with lauric acid has been successfully applied in the quantitative analysis of promethazine in standard serum samples. The influence of several parameters affecting the accumulation step has been investigated such as: pH, ionic strength, interfering ions, paste composition. The detection limit in phosphate buffer at pH 9.0 (tacc = 5 min) has been found to be 1 x 10(-10) M.

Carbon↗
PubMed1988

Electrochemical behaviour of cis-platin at carbon paste and platinum electrodes.

The electrochemical behaviour of a platinum(II) anti-tumour drug (cis-platin) has been investigated at the platinised platinum and carbon paste electrodes using cyclic voltammetry. Measurements performed in neutral aqueous media at the platinised platinum electrode as a function of free chloride ions have enabled the nature of oxidised species to be established and the sensitive determination of the molecule within the range of concentration 1 x 10(-3) - 1 x 10(-5) M to be realised. Use of the carbon paste electrode offers interesting insights into the redox stability of the molecule and allows the hydrolytic degradation of cis-platin to be followed as a function of time.

Journal Article↗