Spectroscopic features of radiolytic intermediates induced in gamma irradiated sulfatiazole: an ESR study

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Abstract

Sulfonamides are used as active ingredients in different drugs to treat infections caused by bacteria. Sulfatiazole (STZ) is one of the commonly used sulfonamides as antibacterial agent in drugs, which constitute potential candidates for radiosterilization. However, the crucial point in this respect is to monitor the amount and characteristic features of the radiolytic intermediates produced after irradiation. Electron spin resonance (ESR) spectroscopy is extensively used for this purpose due to its high sensitivity toward intermediates exhibiting radicalic nature. Thus, the aim of the present work is to investigate the spectroscopic and kinetic features of the species having unpaired electrons induced in gamma irradiated STZ at room and different temperatures in the dose range of 5–50 kGy using ESR spectroscopy. Spectra of irradiated STZ consisted of many resonance peaks in the studied dose and temperature ranges. Heights of the peaks measured with respect to the base line were used to monitor microwave, temperature, time-dependent features of the radical species contributing to the experimental ESR spectra. Four tentative species of different spectroscopic and structural features assigned as A, B, C and D were found well explaining the experimental ESR spectra of gamma irradiated STZ. Comparison between the principal IR bands of unirradiated and gamma irradiated samples showed no detectable changes and appearance of new bands.

Introduction

Gamma radiation has emerged as a useful, efficient and economic tool for sterilization of many drugs in their final containers, and it is more actively used now than at any time (Gopal, 1978, Bhalla et al., 1983, Jacobs, 1995, Reid, 1995). The advantages of sterilization by irradiation include high penetrating power, low chemical reactivity, low measurable residues, small temperature rise and the fact that there are fewer variables to control (Basly et al., 1996, Barbarin et al., 1999, Gibella et al., 2000). However, the adoption of this method requires detailed investigations to ensure that no undesirable changes take place, as ionizing radiation has been reported to cause degradation in the pharmaceuticals and therefore, creating reactive molecular fragments (Miyazaki et al., 1994, Schuler, 1994, Boess and Bögl, 1996), which may result in a toxicological hazard.

Electron spin resonance (ESR) technique appears to be well suited for determination of low concentration of free radicals in complex media and could permit the elucidation of mechanism of radiolysis even for a small radiation dose. Moreover, other features such as high sensitivity, precision, ease and non-destructive readout make ESR superior to other proposed analytical techniques (Onori et al., 1996) to study radiolytic intermediates produced in irradiated solid samples. Previous results have already shown the suitability of ESR for the detection of irradiated drugs and foods (Bögl, 1989, Delincée, 1991, Desrosiers et al., 1991, Raffi et al., 1992, Raffi et al., 1994, Ciranni Signoretti et al., 1993, Ciranni Signoretti et al., 1994, Miyazaki et al., 1994, Raffi, 1998, Basly et al., 1999).

Although STZ is used in the sulfonamide containing drugs at a large extent, the applicability of the sterilization by radiation to the solid drugs containing STZ is not yet investigated in the literature. Therefore, the aims of the present work are: to characterize the radiolytic intermediates carrying unpaired electrons produced in gamma irradiated STZ in the dose range of 5–50 kGy and to explore the potential contribution of ESR technique in investigating the radiosterilization of STZ and/or drug delivery system containing STZ as active ingredient, through a detailed ESR study.

Section snippets

Materials and methods

Sulfatiazole or with its chemical name, 4-amino-N-(thiazol-2-yl)benzenesulfonamide of spectroscopic grade was provided from Faculty of Pharmacy of Hacettepe University (Ankara) and was stored at room temperature in a well-closed container protected from light. No further purification was performed, and it was used as it was received. STZ is a white crystalline powder, which slowly darkens on exposure to light. The melting point of prismatic rods is about 200–204 °C while the other phase forms,

General features of the ESR spectra

Although unirradiated STZ exhibited no ESR signal, samples irradiated at room temperature showed a complex ESR spectrum consisting of 10 resonance peaks. Room temperature spectra recorded for two samples irradiated at two different radiation doses are given in Fig. 2a and b with the assigned peak numbers. The most intense resonance line appearing in the middle of the spectrum was found to have a g value of 2.0045 and a peak to peak width of 5.2 G. Increase in the absorbed dose caused more

Conclusions

Although unirradiated STZ exhibits no ESR signal, samples irradiated at room temperature exhibited a complex ESR spectra consisting of 10 resonance peaks, which saturated as inhomogenously brodened resonance lines in the microwave power range 1–80 mW.

Dose–response curves related with the studied resonance peaks follow exponential increases in the radiation dose range of 5–50 kGy.

Radical species responsible from experimental ESR spectra are unstable at normal (290 K open to air) and stability (313 K

Acknowledgments

We thank Professor Dr. Yekta Özer from Faculty of Pharmacy of Hacettepe University for providing kindly STZ samples of spectroscopic grade.

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