One of the major problems associated with the therapeutic application of β-lactam antibiotics is their significant instability [1]-[3]. Analogs from that group are easily degraded in aqueous solutions and in solid st...One of the major problems associated with the therapeutic application of β-lactam antibiotics is their significant instability [1]-[3]. Analogs from that group are easily degraded in aqueous solutions and in solid state, which happens predominantly as a result of β-lactam ring chemical degradation. Because of this, the chemical integrity of β-lactam antibiotics must be closely monitored to meet FDA requirements. The original iodometric method based on visual detection of the end products of beta-lactamase hydrolysis that has been used to test beta-lactamase activity [4] was modified to quantitatively assess the amount of degraded product in amoxicillin. A UV-visible spectrophotometric method has been used, focusing on the ability of the products from the degradation of β-lactam analogs to absorb iodine from bulk solution, resulting in a significant reduction in the absorption spectra. Amoxicillin trihydrate tablets with different expiration dates and amoxicillin samples pre-loaded with known amounts of degraded amoxicillin have been used to generate a calibration curve and quantify the presence of degraded materials. Results show that the changes in the absorption spectra of iodine reagent directly correlate with the fraction of degraded β-lactam antibiotics, such as amoxicillin, in commercial products. The proposed assay might be as close as one step from simpler and cheaper methods of quantitative analysis of degraded β-lactam analogs, with estimated sensitivity in the range of 1% - 2%, which is better than the current FDA requirements.展开更多
The effect of UV- and 137Cs gamma radiation on the structural and chemical integrity of human hair was studied to determine the feasibility of using human hair as a non-invasive biomarker of radiation exposure to ioni...The effect of UV- and 137Cs gamma radiation on the structural and chemical integrity of human hair was studied to determine the feasibility of using human hair as a non-invasive biomarker of radiation exposure to ionized gamma- and non-ionized UV-radiation. Steady state tryptophan (Trp) fluorescence and chemical analytical methods were used to evaluate the molecular integrity of Trp fluorophores and SH-groups in hair proteins and to assess the radiation induced damage quantitatively. It was found that human hair fibers were progressively damaged by exposure to both UV- and ionized gamma radiation. Damage to the hair was evidenced by a decrease in the fluorescence intensity as a result of observed depletion of the amino acid tryptophan as well as significant reduction in a number of free SH-groups in hair proteins. Hair damage was dose-dependent for exposures between 0 and 10.0 Gy and 0 - 20 J/cm2 of UV-radiation. Additional results demonstrate that hair-fibers exposed to gamma rays, with much higher quantum energy than UV, undergo a smaller extent of changes in Trp fluorescence than when exposed to lower or equal energy of UV-irradiation. The stable Trp fluorophore appears to be extremely sensitive to UV-radiation in contrast to the ionized gamma radiation whose damage is originated from the reaction of free radicals and direct deposition of energy. We conclude that fluorescence spectroscopy represents a useful tool in the quantitative evaluation of the radiation exposure and could also be used for the rapid and non-invasive assessment of radiation dose i.e. biodosimeter. The approach is simple, non-invasive and appears to have considerable potential that enables quantitative evaluation of radiation dose exposure in a single hair fiber.展开更多
文摘One of the major problems associated with the therapeutic application of β-lactam antibiotics is their significant instability [1]-[3]. Analogs from that group are easily degraded in aqueous solutions and in solid state, which happens predominantly as a result of β-lactam ring chemical degradation. Because of this, the chemical integrity of β-lactam antibiotics must be closely monitored to meet FDA requirements. The original iodometric method based on visual detection of the end products of beta-lactamase hydrolysis that has been used to test beta-lactamase activity [4] was modified to quantitatively assess the amount of degraded product in amoxicillin. A UV-visible spectrophotometric method has been used, focusing on the ability of the products from the degradation of β-lactam analogs to absorb iodine from bulk solution, resulting in a significant reduction in the absorption spectra. Amoxicillin trihydrate tablets with different expiration dates and amoxicillin samples pre-loaded with known amounts of degraded amoxicillin have been used to generate a calibration curve and quantify the presence of degraded materials. Results show that the changes in the absorption spectra of iodine reagent directly correlate with the fraction of degraded β-lactam antibiotics, such as amoxicillin, in commercial products. The proposed assay might be as close as one step from simpler and cheaper methods of quantitative analysis of degraded β-lactam analogs, with estimated sensitivity in the range of 1% - 2%, which is better than the current FDA requirements.
文摘The effect of UV- and 137Cs gamma radiation on the structural and chemical integrity of human hair was studied to determine the feasibility of using human hair as a non-invasive biomarker of radiation exposure to ionized gamma- and non-ionized UV-radiation. Steady state tryptophan (Trp) fluorescence and chemical analytical methods were used to evaluate the molecular integrity of Trp fluorophores and SH-groups in hair proteins and to assess the radiation induced damage quantitatively. It was found that human hair fibers were progressively damaged by exposure to both UV- and ionized gamma radiation. Damage to the hair was evidenced by a decrease in the fluorescence intensity as a result of observed depletion of the amino acid tryptophan as well as significant reduction in a number of free SH-groups in hair proteins. Hair damage was dose-dependent for exposures between 0 and 10.0 Gy and 0 - 20 J/cm2 of UV-radiation. Additional results demonstrate that hair-fibers exposed to gamma rays, with much higher quantum energy than UV, undergo a smaller extent of changes in Trp fluorescence than when exposed to lower or equal energy of UV-irradiation. The stable Trp fluorophore appears to be extremely sensitive to UV-radiation in contrast to the ionized gamma radiation whose damage is originated from the reaction of free radicals and direct deposition of energy. We conclude that fluorescence spectroscopy represents a useful tool in the quantitative evaluation of the radiation exposure and could also be used for the rapid and non-invasive assessment of radiation dose i.e. biodosimeter. The approach is simple, non-invasive and appears to have considerable potential that enables quantitative evaluation of radiation dose exposure in a single hair fiber.
