Mara M. Aleksić

Recent Developments in Electroanalytical Chemistry of Cephalosporins and Cefamycins

Cephalosporins (I, R4 = H) and cefamycins (I, R4 = OCH3) are antibiotics with a broad spectrum of antimicrobial and antibacterial properties. These compounds contain a β-lactam ring which is fused with a six-membered dihydrothiazine ring bearing substituents R1 and R2 in the side-chains at C-3 and C-7 (I)(Table I).

Two-step reduction of the O-methyloxime group in the antibiotic cefetamet

Abstract Most oximes as well as their N-alkyl and O-alkyl derivatives are electrochemically reduced in a single four-electron step to the amine. Some exceptions have been reported, where the reduction occurs in two two-electron steps. The reduction of the O-methyloxime grouping in the antibiotic cefetamet occurs at pH 5–9 in two steps, corresponding to a reduction to the imine and amine, respectively. It has been shown that the separation of the two two-electron processes is caused by differences in position and rate of establishment of acid–base equilibria resulting in protonations of the oxime and imino grouping.

Voltammetric methods for analytical determination of fleroxacin in Quinodis® tablets

The direct current (dc) and differential pulse (dp) polarographic reduction of fleroxacin was done in a wide pH range from 2.48 to 13.00. The appropriate buffer choice was made for its dp polarographic determination in a range from 1.845 to 16.926 microg /ml, at pH 8.50. The adsorptive properties of fleroxacin were investigated in order to achieve an increase in sensitivity and a possibility of fleroxacin determination by applying the adsorptive stripping voltammetric method. The adsorptive processes at the hanging mercury drop electrode were investigated in Britton-Robinson and borate buffers. Adsorptive preconcentration followed by differential-pulse cathodic stripping showed one wave at approximately - 1.1 V being the most sensitive for analytical determination of fleroxacin. Two linear ranges were obtained, the first one from 18.465 to 258.51 ng/ml, and the second one from 3.693 to 18.465 ng/ml.

Simultaneous determination of cefotaxime and desacetylcefotaxime in real urine sample using voltammetric and high-performance liquid chromatographic methods

Two rapid, accurate and sensitive methods are developed and validated for the quantitative simultaneous determination of cefotaxime (CFX) and its active metabolite desacetylcefotaxime (DCFX) in urine. Based on the previous results which showed the four electron reduction of CFX at approximately -0.5 V, and the new findings that DCFX reduction occurred at more positive potential (-0.23 V), the new adsorptive stripping differential pulse voltammetric (AdSDPV) method was developed for determination of CFX in the presence of DCFX. Linear responses were observed over a wide concentration range (0.07-0.52 microg/ml for CFX and 0.22-1.3 microg/ml for DCFX) in urine. The second assay involves subsequent separation on a reversed-phase HPLC column, with ultraviolet detection at 262 nm. Retention times were 4.057 and 1.960 min for CFX and DCFX, respectively. Linear responses were observed over a wide range, 0.55-6.60 microg/ml for CFX and 1.10-11.00 microg/ml for DCFX, in urine. The statistical evaluation for both methods was examined by means of within-day repeatability (n=5) and day-to-day precision (n=3) and was found to be satisfactory with high accuracy and precision.

Adsorptive stripping voltammetric determination of cefetamet in human urine.

On the basis of previously established mechanism of cefetamet (CEF) reduction, two methods were suggested for CEF determination-differential pulse polarographic and differential pulse adsorptive stripping voltammetric method. Two pH values were chosen, 2.0 and 8.4, where the electrochemical process was defined as one four-electron and two two-electron processes, respectively. The methods were performed in Britton-Robinson (BR) buffer and the corresponding calibration graphs were constructed and statistical parameters were evaluated. Applying the AdSV method at pH 2.0 linearity was achieved from 2 x 10(-8) to 2 x 10(-7) M with limit detection and limit determination of 4 x 10(-9) and 1.4 x 10(-8) M, respectively. At pH 8.4, the linearity was obtained between 6 x 10(-8) and 6 x 10(-7) M, with limit detection and limit determination of 1.5 x 10(-8) and 5 x 10(-8) M, respectively. Since the AdSV method enabled lower concentrations of CEF to be determined, this method was tested for CEF determination in spiked urine samples, and DPP method was used as a comparative one.

The use of limiting currents in determination of the effect of viscosity in electrochemical experiments performed in mixtures of water with some organic co-solvents

Ratios of limiting diffusion controlled currents recorded in aqueous solutions to those obtained in mixture with water-soluble organic co-solvents yield values of ηrel1/2. These values can be used for evaluation of electrochemical experiments in such media and for distinguishing currents affected solely by a change in viscosity from those caused by other solvent–solute interactions, e.g. covalent additions. Limiting currents of Cd2+ ions and of 2-hydroxy-1,4-naphthoquinone proved to yield most reliable results, values of ηrel1/2 obtained with Tl+ ions showed somewhat poorer correlation. The average values of ηrel1/2 obtained from comparison of limiting currents for mixtures of water with ethanol and acetonitrile are in very good agreement with average values of ηrel1/2 reported in the literature and in acceptable agreement for mixtures of water with 2-propanol. Nevertheless, the electrochemical data show much smaller standard deviations, than the data reported in the literature, which have shown inconsistencies when data from different sources are compared and can be considered as more reliable. The data obtained for mixtures of water with DMF have not been previously reported.

Application of Adsorptive Stripping Voltammetry for the Determination of Selected Methoxyimino Cephalosporins in Urine Samples

In last two decades different electroanalytical methods are used for sensitive and selective determination of cephalosporins. In this paper the electrochemical behavior of methoxyimino cephalosporins, reduction mechanism and nature of the process at the mercury electrode surface is presented. Special attention is paid to the cephalosporins adsorption at the mercury surface. Based on this phenomenon, the adsorptive stripping methods are established for determination of low concentration of these drugs in urine samples, both in-vitro, and in-vivo conditions. The application of the adsorptive stripping differential pulse voltammetry (AdSDPV) for determination of cefpodoxime proksetile (CP), cefotaxime (CF), desacetylcefotaxime (DCF) and cefetamet (CEF) is summarized. The best sensitivity of determination in-vitro in urine was achieved for CP, in acid solutions (LOD 7.410(-9)M and LOQ 2.410(-8)M), followed by CF, CEF and DCF. This is in accordance with the strength of their adsorption. Determination of CF and DCF by AdSDPV in-vivo is also presented. Compared to other analytical methods, AdSDPV showed advantages in simplicity of the sample preparation, and over the other voltamperometric methods, higher sensitivity and selectivity.