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The radicals were studied by electron paramagnetic resonance EPR spectroscopy using an X-band spectrometer 9. After gamma irradiation, complex EPR lines were recorded confirming the presence of a large number of free radicals formed during the irradiation. For all tested antibiotics, concentrations of free radicals and parameters of EPR spectra changed with storage time. In modern medicine, a number of sterilization methods are applied, including tempering, cauterization, hot air sterilization, steam sterilization, sterile filtration, radiation sterilization e.
In the case of medical substances, choice of the sterilization method depends on the type, properties, and production method of the substance in question. Irradiation of drugs, or other medical products, by a suitable dose of ionizing radiation, conducted in an appropriate environment, ensures sterile conditions Basly et al.
Radiation sterilization is especially useful in the case of thermolabile products, because irradiation causes only a small rise in the temperature of sterilized substances Basly et al. Moreover, packaged products may also be irradiated as gamma radiation possesses excellent penetrative properties; this constitutes one of its economic advantages Basly et al. In the present study, the penicillin-derived antibiotics, such as piperacillin, ampicillin, and crystalline penicillin, were used.
All investigated antibiotics were supplied by Sigma-Aldrich. Three samples of each antibiotic were irradiated. All samples were located at optimal distance from the radiation source so that the dose gradient did not affect the homogeneity of the dose absorbed by the sample volume. EPR spectra were recorded in the form of the first-derivative absorption by 2-mW microwave radiation, where microwave saturation cannot be observed.
Maximal errors of the analyzed parameters are given in brackets. The values of amplitude and integral intensity of the EPR lines correspond to the number of paramagnetic centers in the sample. The amplitude was determined by the identification of the peak-to-peak of the first derivative of the EPR lines, while the integral intensity was determined by double integration of the EPR lines, which corresponds to the area under the curve of the absorption of microwaves.
The concentration of free radicals N in the tested antibiotics was calculated using the following formula:. As the area under the absorption curve is proportional to the number of paramagnetic centers, the results of double integration of the first-derivative EPR signal were compared with those of the standard, and the number of paramagnetic centers per gram was determined for every sample. Ultramarine sodium aluminosilicate—g-factor 2. The wings of the ultramarine spectrum are Gaussian in shape.
All samples were stored in thin-walled, open quartz tubes. One- and two-exponential functions were used to analyze time patterns of EPR parameters:. A characteristic feature of the adopted error criterion is to reduce the impact of large individual differences—outliers analysis so-called Manhattan distance.
In contrast, if the usual least squares procedure is applied where the differences are squared, a single large difference would significantly affect the result. Penicillin exerts its therapeutic effect by inhibiting the synthesis of bacterial walls. Because it is effective only against those cells that synthesize peptidoglycan, it is not toxic to humans Janiec Chemical structure of the studied antibiotics: piperacillin a , ampicillin b , and crystalline penicillin c Zejc and Gorczyca Identification and dosimetry of paramagnetic centers in gamma-irradiated penicillin-derived antibiotics.
The asymmetry of the vancomycin EPR spectra indicates their complex structure. EPR spectra of the unirradiated and irradiated penicillin-derived antibiotics piperacillin a , b , ampicillin c , d , and crystalline penicillin e , f. EPR spectra were recorded on the same day when the gamma irradiation was performed. EPR spectra of a complex shape are observed for many irradiated medical substances Basly et al. The reason for a complex shape of EPR spectra is the presence of several groups of free radicals Basly et al.
Additionally, EPR lines of different types of free radicals are usually close to each other since their values of the magnetic field resonant induction are not much. Thus, the corresponding EPR lines overlap and it is difficult to identify them in the actually measured sum spectrum.
Nevertheless, the measured spectra suggest the presence of more than one type of free radicals in the penicillin-derived antibiotics: piperacillin, ampicillin, and crystalline penicillin irradiated in the present study. Numerical analysis of the time dependence of the integral intensity Fig. Time influence of sample storage on integral intensities I of EPR lines after gamma irradiation for piperacillin, ampicillin, and crystalline penicillin.
Time influence of sample storage on amplitudes A of EPR lines after gamma irradiation for piperacillin, ampicillin, and crystalline penicillin. More specifically, this decrease may be due to the formation of quasi-chemical complexes between the free radicals of the sample and the paramagnetic molecules of oxygen O 2. Pairing the spins of a free radical and an oxygen molecule causes the observed decrease in the intensity of EPR lines. Note that formation of quasi-chemical complexes between oxygen and a paramagnetic sample has been described in the literature Pryor Presumably, the rapid decrease in the amount of free radicals in the first phase of samples storage corresponds to the interaction of oxygen with paramagnetic centers on the surface of the sample, where the oxygen supply is the best.
From the average g-factor values, the type of free radicals that are present in the samples can be determined. The g-values did not vary with storage time of the samples. In contrast, the concentrations of free radicals and EPR spectra parameters did change in all samples as a function of storage time. Storage time did not affect the line widths of piperacillin and crystalline penicillin samples, whereas there was a small increase with time for ampicillin Fig.
In contrast, there was no change in the color of the samples during their storage. After dissolving the samples in water, the re-dried antibiotics underwent slight color change, but did not return to the original color.
A higher concentration of radicals generated at the same absorbed dose of gamma radiation indicates a higher radiation sensitivity. In this context, however, the efficiency of microcrystalline matrices of trapping paramagnetic centers must also be considered. The present results suggest that dissolving the gamma-sterilized drug in water results in a rapid disappearance of free radicals.
This may be due to the release of the paramagnetic centers from the crystal lattice of the drug and their recombination. From the pharmacological point of view, the biochemical properties of intermediates generated in drugs following gamma sterilization are important if they are formed in a significant number and therefore reduce the therapeutic properties of the pharmaceuticals. Free radicals formed in sterilized drugs may have an effect not only on the pharmacological activity of the drug Polat and Korkmaz , but also on its pharmacokinetic properties Gibella et al.
Unfortunately, it is not possible to predict the influence of ionizing radiation on the stability of radicals even if the considered compounds are similar, because even minor changes in molecular structure may have a significant influence on processes observed by EPR spectroscopy Polat and Korkmaz As expected, even though they belong to the same group of antibiotics, the sterilized substances investigated in the present study show very different properties under the influence of gamma radiation.
EPR spectra of the all analyzed irradiated antibiotics were complex in shape, demonstrating the existence of more than just one type of paramagnetic center.
It has been proven here that the concentration of free radicals in the irradiated antibiotics decreases during storage Figs. Phase 1 corresponds to surface recombination, while phase 2 to solid diffusion. In the case of a large number of paramagnetic centers and a short distance between them during the first phase of storage , the possibility of a fast recombination of paramagnetic centers should also be considered.
It is assumed that the interaction between free radicals and oxygen molecules O 2 , i. The creation of quasi-chemical complexes between oxygen and radicals has already been described in the literature Najder-Kozdrowska et al.
In the present study, investigations using the EPR method have shown that free radicals in gamma-irradiated antibiotics are located in close proximity to each other. The values of EPR line widths for all tested antibiotics 0.
In general, wide EPR lines exist in the case of strong dipole spin—spin interactions and are characteristic for short distances of non-paired electrons of free radicals in the sample. The widening of EPR lines due to dipole interactions is caused by the statistical decay of the magnetic field in a sample Pilawa et al. The constant K 0 A , I indicates the concentration of free radicals in an irradiated drug sample after a long storage time.
In the case of piperacillin, ampicillin, and crystalline penicillin, the constant K 0 I was 0. It can be also assumed that the exponent of the exponential function determines the number of types of free radicals in the samples.
For the investigated samples piperacillin, ampicillin, and crystalline penicillin , it is concluded that there are two types of paramagnetic centers, which is also confirmed by the complex nature of the spectrum. Read article at publisher's site DOI : Free to read.
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Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI: In clinical practice for the treatment of obesity, several natural macromolecular compounds are used, whose operation is based on supporting weight loss. During the use of dietary supplements containing chitosan, disease sometimes occurs and treatment for this often comprises different therapeutic agents and antibiotics. View PDF. Save to Library.
Antybiotykoterapia Praktyczna - Część II - Kompendium Antybiotyków
The aim of this work was to determine the concentrations and properties of free radicals in piperacillin, ampicillin, and crystalline penicillin after gamma irradiation. The radicals were studied by electron paramagnetic resonance EPR spectroscopy using an X-band spectrometer 9. After gamma irradiation, complex EPR lines were recorded confirming the presence of a large number of free radicals formed during the irradiation. For all tested antibiotics, concentrations of free radicals and parameters of EPR spectra changed with storage time. In modern medicine, a number of sterilization methods are applied, including tempering, cauterization, hot air sterilization, steam sterilization, sterile filtration, radiation sterilization e.
THE ADSORPTION OF SIMVASTATIN ON CHITOSANS IN AN IN VITRO PHARMACEUTICAL MODEL