Radiostability of florfenicol in the solid state.
The effect of ionizing radiation on florfenicol (FF), an antibiotic with wide antibacterial properties was investigated to determine whether it can be sterilized using high-energy radiation. FF was irradiated by E-beam radiation to doses of 25-800 kGy, and then changes in the physico-chemical properties were examined using chromatographic methods (TLC and HPLC), spectroscopic methods (NMR and MS) and hyphenated methods (HPLC-MS). It was found that a standard sterilizing dose of 25 kGy led to the formation of two new products of radiolysis as well as lowering the content of FF by 0.95%. With higher doses of radiation, the content of FF further decreased (by 12.27% with a dose of 800 kGy), and new products of radiolysis appeared (up to five with a dose of 800 kGy). However, there were no differences between the NMR and MS spectra of irradiated and non-irradiated samples of FF. A linear dependence was found between the dose of radiation and the FF content (correlation coefficient of 0.9951) as well as between the melting point and the sum of products of radiolysis (correlation coefficient of 0.9975). It was found that a radiodegradation of FF took place by the breaking of an amide bond, leading to the formation of an aliphatic amine, which was subsequently oxidized to 4-methylsulfonylbenzoic acid. The radiolytic yield for the radiodegradation of FF was calculated to be 10.24 molecules/100 eV for a dose of 25 kGy. As a result of our investigation, we can conclude that FF shows a reasonably good radiostability in the range of doses used for sterilization, i.e. 25 kGy and below, and therefore it can be sterilized using high-energy radiation without changing its physicochemical, properties and hence its therapeutic efficacy.
Marciniec
Barbara
B
Department of Pharmaceutical Chemistry, Karol Marcinkowski University of Medical Sciences, 6 Grunwaldzka, 60-780 Poznań, Poland. bmarcin@ump.edu.pl
Stawny
Maciej
M
Kachlicki
Piotr
P
Jaroszkiewicz
Ewa
E
Needham
Michael
M
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000528:radiation effects*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003116:Color; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D013839:Thiamphenicol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000528:radiation effects
D000900:Anti-Bacterial Agents; C035534:florfenicol; D013839:Thiamphenicol