Stability studies on florfenicol using developed derivative spectrophotometric methods.

OBJECTIVES: This study aims to investigate the stability of florfenicol using previously developed derivative spectrophotometric methods (D1 and D2). METHODS: The studied stability-indicating pararmeters included alkali (NaOH, 1M), acid (HCl, 1M), pH changes (buffer pH 2.2-11), temperature (80°C and 100°C at pH 10) and light. RESULT: A constructed pH profile for the drug degradation rate revealed a significant effect of pH on the drug stability between pH ranges 8 and 11. The obtained profile indicated first order dependence of Kobs on [OH-]. Arrhenius plot at pH 10 was found linear at temperatures 80°C and 100°C with estimated activation energy of 19.35kcal/mol. The calculated rate constant (Kobs), t½ and t90 at 25°C were found to be 1.8×10-3h, 385h and 58.3h, respectively. The photostability of florfenicol was also studied by exposing the drug solution to direct sunlight during mid-day time. CONCLUSION: The obtained results reflected the instability of florfenicol under the study conditions.

Degradation of florfenicol in water by UV/Na2S 2O 8 process.

UV irradiation-activated sodium persulfate (UV/PS) was studied to degrade florfenicol (FLO), a phenicol antibiotic commonly used in aquaculture, in water. Compared with UV/H2O2 process, UV/PS process achieves a higher FLO degradation efficiency, greater mineralization, and less cost. The quantum yield for direct photolysis of FLO and the second-order rate constant of FLO with sulfate radicals were determined. The effects of various factors, namely PS concentration, anions (NO3 (-), Cl(-), and HCO3 (-)), ferrous ion, and humic acid (HA), on FLO degradation were investigated. The results showed that the pseudo-first-order rate constant increased linearly with increased PS concentration. The tested anions all adversely affected FLO degradation performance with the order of HCO3 (-) > Cl(-) > NO3 (-). Coexisting ferrous ions enhanced FLO degradation at a Fe(2+)/PS molar ratio under 1:1. HA significantly inhibited FLO degradation due to radical scavenging and light-screening effect. Toxicity assessment showed that it is capable of controlling the toxicity for FLO degradation. These findings indicated that UV/PS is a promising technology for water polluted by antibiotics, and the treatment is optimized only after the impacts of water characteristics are carefully considered.

Identification of radiolysis products of solid thiamphenicol.

Spectroscopic and chromatographic methods (HPLC, HPLC-MS, NMR) were used to observe, separate and identify products of radiolysis of thiamphenicol (TF), irradiated in the solid state at room temperature and atmospheric pressure with an electron beam from a linear accelerator to doses between 25 and 800 kGy. Nine products of radiolysis of thiamphenicol were identified, among them were TF amine, dichloroacetic acid, 4-methylsulfonylbenzoic acid, demono- and dedichloroderivative of TF, 2,2-dichloro-N-{3-hydroxy-1-[4-(methylsulfonyl)phenyl]-1-oxopropan-2-yl}acetamide and 3-({1,3-dihydroxy-1-[4-(methylsulfonyl)phenyl]propan-2-yl}amino)-3-oxopropanoic acid. The process of radiodegradation of TF was proposed as consisting of several parallel primary reactions (dehalogenation, oxidation of the OH group at C(1), hydrolysis of the amide bond, a rapture of the C(2)-C(3) bond of propan-1-ol) and secondary reactions (carboxylation and oxidation). The use of high doses, well above the sterilization dose of 25 kGy, allowed observation of changes of TF content as a function of radiation dose, calculation of radiolytic yield (G(-TF)) and kinetic parameters of the degradation reaction. It was found that the standard sterilizing dose lowers the content of TF by only 0.1% and the radiolytic efficacy of the process of radiodegradation is 0.76 molecules/100eV. Further increase in the dose lowers the content of TF to 92.1% for 800 kGy dose and leads to an increase in the value of G(-TF). It was also found that the summative process of radiodegradation of TF exposed to a beam of electrons of 10 kGy/s follows the first order reaction kinetics with a degradation constant of k=0.001s(-1). On the basis of the experiments conducted it can be stated that the radiolysis of TF in the presence of an E-beam, in substantia, follows multidirectional course in the same way as radiolysis of chloramphenicol. TF exposed to the standard sterilizing dose of 25 kGy degrades only by 0.1%, the amount acceptable by the ICH, and forms only one product of radiolysis (TF amine) and therefore we conclude that it can be sterilized by ionizing radiation under the conditions described above.

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.