Zbigniew Fijalek

Contribution to the understanding of the reduction mechanism of nitrobenzene

Electrochemical reduction of nitrobenzenes has been studied extensively [1,2]. For the processes involved Haber [3] proposed a scheme which is generally accepted in a modified form [4,5]. Nitrobenzene was the first organic compound for which a current-voltage curve obtained with the dropping mercury electrode was reported [6]. At this electrode, where, because of the continuous surface renewal the short contact period excludes accumulation and side-reaction of products [7], the reduction occurs in a single four-electron step. In acidic media the monoand di-protonated forms of arylhydroxylamine [8-lo] formed in the first step are reduced at more negative potentials in a second, two-electron step. The overall four-electron process involves also a transfer of four protons (reaction 1): ArNO,+4e-+4H++ArNHOH+H,O (1) The sequence of transfer of protons and electrons cannot be deduced in aqueous media from the variation in the limiting current of the first step, as this is pH-independent. Mechanistic studies in non-aqueous media [11,12] do not offer information about the process in aqueous solutions because of the difference in solvation of all the species involved and in their acid-base properties. Similarly for mechanistic studies in the presence of surfactants [13-151 the role of micelles and other specific effects of adsorbed surfactants cannot be excluded. The first type of experimental evidence that can be used in the elucidation of the sequence of electron and proton transfer is the fact that the sequential reduction of the nitro group to a nitroso and a hydroxylamino group has never been reported to occur in two two-electron steps. The presence of a single four-electron wave

Determination of atracurium, cisatracurium and mivacurium with their impurities in pharmaceutical preparations by liquid chromatography with charged aerosol detection.

The Corona CAD (charged aerosol detection) is a new type of detector introduced for LC applications that has recently become widely applied in pharmaceutical analysis. The Corona CAD measures a physical property of analyte and responds to almost all non-volatile species, independently of their nature and spectral or physicochemical properties. The LC method with charged aerosol detection was developed for the determination of three isomers of atracurium, cisatracurium and also three isomers of mivacurium with their impurities. The limit of quantitation for laudanosine was 1 microg ml(-1). The elaborate method for the analysis of those active substances and laudanosine proved to be fast, precise, accurate and sensitive. All other impurities were identified using time-of-flight mass spectrometry with electrospray ionization.

Determination of Gentamicin Sulphate Composition and Related Substances in Pharmaceutical Preparations by LC with Charged Aerosol Detection

A new, simple and repeatable liquid chromatography method with charged aerosol detection (LC-CAD) for the determination of gentamicin sulphate composition and related substances has been developed. Gentamicin lacks of chromophores, therefore its determination is quite problematic. Using a universal CAD enables to achieve good separation without sample derivatization. Mass spectrometry was employed to confirm the LC-CAD peak profile. The proposed method was validated and applied for the determination of gentamicin sulphate composition and related substances in pharmaceutical preparations.

Determination of pipecuronium bromide and its impurities in pharmaceutical preparation by high-performance liquid chromatography with coulometric electrode array detection

A sensitive and selective HPLC method with coulometric electrode array detection for the determination of pipecuronium bromide and its four impurities has been developed. The coulometric electrode array detection at increasing potentials from +300 to +900mV of the porous graphite electrode versus the palladium reference electrode was used. The limit of detection and quantitation for pipecuronium bromide was 8 and 25ngml(-1), respectively. This elaborate method for the simultaneous analysis of pipecuronium bromide and its impurities proved to be fast, precise, accurate, sensitive, and could be applied to analysis in substances and in pharmaceutical preparations.

Determination of Methimazole and Carbimazole Using Polarography and Voltammetry

Abstract Anodic waves of methimazole (I) (1-methylimidazole-2-thiol) and carbimazole (II) (1-ethoxycarbonyl-3-methyl-2-thio-4-imidazoline) on mercury electrodes correspond to mercury salt formation. Both compounds form in the thiono form a soluble complex at pH < 6, compound (I) at higher pH-values a slightly soluble salt of the thiol form. Electrode processes involving the thiol form are complicated by adsorption. Oxidation at solid electrodes occurs only at potentials more than 0.5 V more positive. For compound (I) spectrophotometry indicated pKa=12.0 ± 0.2. By d.c. polarography in 0.1 M H2SO4 containing 10% ethanol the determination of both compounds is possible between 4 × 10− and 1 × 10−3 M, by differential pulse polarography between 1 × 10− and 1 × 10−4 M, by differential pulse voltammetry at HMDE between 5 × l0−7 and 6 × 10− M.

Selenitetriglicerydes affect CYP1A1 and QR activity by involvement of reactive oxygen species and Nrf2 transcription factor

Selenitetriglycerides are a group of compounds that contain selenium (Se) (IV). In this paper, we present the results of examinations of three structurally-related selenitetriglicerydes that contain various Se concentrations: 2%, 5% and 7% Selol. The present study concentrates on the effect of Selol on phase 1 and 2 enzyme activity and the implications of free radicals and the nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway in the activity of this compound. The cytotoxic and cytostatic activities of the three kinds of Selol were evaluated; however, the cytotoxic effect was observed only for 7% Selol. Our results show that 2% Selol acts as a monofunctional inducer of phase 2 enzyme activity, and the induction is mediated by the Nrf2 transcription factor. Selol 7% acts in an opposite manner and induces phase 1 with simultaneous inhibition of phase 2 enzyme activity. The differential effect can be associated with the increase in Se content, leading to a change in the structure of the compound.

Application of high-performance liquid chromatography with amperometric and coulometric detection to the analysis of SZ1677, a new neuromuscular blocking agent, and its two derivatives.

A HPLC method with amperometric and coulometric detection for the determination of SZ1677 and its two derivatives SZ1676 and SZ1823 has been developed. This active substance is under development (clinical trial) and there are no analytical methods published for the determination of SZ1677 thus far. The limit of quantitation for SZ1677 was 25 and 100 ng ml(-1) by the coulometric and amperometric detection, respectively. The elaborate method for the simultaneous analysis of SZ1677 and its two derivatives proved to be fast, precise, accurate and sensitive.

Polarographic and spectrophotometric study of the base catalyzed hydrolysis of carbimazole

Abstract Carbimazole (1-ethoxycarbonyl-3-methyl-2-thio-imidazoline) undergoes at pH > 9 hydrolysis. The resulting carboxylate is rapidly decarboxylated and produces l-methylimidazole-2-thiol. Kinetics of hydrolysis was followed by decrease of concentration of the starting ester spectrophotometrically and by increase in concentration of produced thiol polarographically. Good agreement of rate constants and their dependence on [OH−] indicates that decarboxylation is rapid. Hydrolysis is assumed to follow a BAC2 mechanism, high reactivity in decarboxylation is attributed to a formation of a highly reactive zwitterion as intermediate.

Cyclic voltammetry and quartz crystal microbalance electrochemical studies on thiosalicylic acid and dithiodibenzoic acid

ABSTRACT Cyclic voltammetry (CV) and electrochemical quartz crystal microbalance (EQCM) were used to study the behavior of thiosalicylic acid (KTS) and dithiodibenzois acid (DTDB) at the controlled-growth mercury drop electrode (CGMDE), at the gold electrode, and at the carbon electrode. The CV method was used to study peak current intensities and peak potentials in relation to pH of the solution, to scan rate and to the concentration of the analyte. Optimum measurement parameters were established and stock solutions developed. The electrode activity was found to be primarily due to the oxidation of the sulhydryl group. The currents observed are diffusion controlled. Electrochemical studies on complexes of KTS with Cu(II) were undertaken at varying constituent proportions and the cathodic peak was found to rise by ca. 70% whereby the sensitivity of the determination was considerably increased. The EQCM method allowed to establish that, as KTS is oxidized, the electrode slightly gains in weight (ca. 80 ng). As DTDB is reduced, the electrode slightly looses in weight (ca 40 ng). Studies on the equimolecular KTS-Cu(II) complex showed the electrode to gain about 125 ng more in weight than in the solutions containing KTS alone, a fact evidencing for the formation of the complex and for its deposition on the electrode surface. A procedure was developed to determine KTS and DTDB in the substance by the CV method. Statistical evaluation of data showed the results to be characterized by good accuracy and precision (RSD 0.80% and 0.61%, respectively).

Voltammetric and electrochemical quartz crystal microbalance studies of sulforaphane and its Zn(II) complexes

Cyclic voltammetry (CV) and electrochemical quartz crystal microbalance (EQCM) methods were used to study the behavior of sulforaphane (SFR). To established electrochemical properties of SFR methyl-, ethyl-, 2-chloroethyl-, propyl-, butyl- and tert-butyl-isothiocyanates were examined at gold electrode. Optimal measurement parameters were established and stock solutions developed. The electrode activity of the studied compounds (cathodic peak E(p)=-0.6 V) was found to be primarily due to the oxidation of the isothiocyanate group. By the EQCM method it was found that during the reduction of SFR the mass of the electrode systematically increased in successive scans by ca. 120 ng per scan and in the mixture of SFR and Zn(2+) ions ca. 350 ng. Formation of SFR complexes with Zn(2+) ions was confirmed by EQCM and UV methods. Cyclic voltammetric method has been elaborated for SFR determination and compared with UV method.