LC/MS/MS study for identification of entacapone degradation product obtained by photodegradation kinetics.

Entacapone is indicated for clinical use as an adjunct to levodopalcarbidopa to treat patients with idiopathic Parkinson's Disease who experience the signs and symptoms of end-of-dose wearing-off. The aim of this study was to determine the photodegradation kinetics and to elucidate the structure of the main degradation product. The stability of entacapone was studied in order to investigate the degradation kinetics of this drug using LC as a stability indicator. Entacapone was subjected to accelerated photodegradation. This study was carried out with methanolic solutions, prepared from coated tablets, in quartz cells under UV light at 254 nm. The degradation process of entacapone in solutions can be described by second-order kinetics under the experimental conditions used in this study. The LC/MS/MS determinations revealed that in the above conditions the photodegraded product formed the geometric isomer of entacapone (Z-entacapone). The obtained results show the importance of appropriate light protection during the drug development process, storage, and handling.

Interactions of ozone with organic surface films in the presence of simulated sunlight: impact on wettability of aerosols.

Heterogeneous reactions between organic films, taken as proxies for atmospheric aerosols, with ozone in presence of simulated sunlight and the photosensitizer 4-carboxybenzophenone (4-CB) were observed to alter surface properties as monitored by contact angle during the reaction. Attenuated total reflectance Fourier transform infrared spectroscopy (FTIR-ATR) was used in addition for product identification. Two types of model surfaces were systematically studied: 4-CB/4-phenoxyphenol and 4-CB/catechol. Solid organic films made of 4-CB/catechol were observed to become hydrophilic by simultaneous exposure to ozone and simulated sunlight, whereas organic films made of 4-CB/4-phenoxyphenol become hydrophobic under the same conditions. These changes in contact angle indicate that photo-induced aging processes involving ozone (such as oligomerisation) not necessarily favour increased hygroscopicity of organic aerosols in the atmosphere. The ratio between hydrophobic and hydrophilic functional groups should reflect the chemical property of organic films with respect to wettability phenomena. Contact angles and surface tensions of the exposed organic film made of 4-CB/4-phenoxyphenol were found to correspond to the hydrophobic/hydrophilic ratios obtained from the FTIR-ATR spectra.

Photocatalytic cleavage of single TiO2/DNA nanoconjugates.

TiO(2)/DNA nanoconjugates were successfully fabricated by using the catechol moiety as a binding functional group, which was confirmed by steady-state absorption and fluorescence spectroscopies. Upon UV irradiation, the photocatalytic cleavage of the TiO(2)/DNA nanoconjugates was observed at the single-molecule level by using wide-field fluorescence microscopy. The decrease in the number of conjugates, which was estimated from the luminescent spots due to semiconductor quantum dots modified at the DNA strand, was significantly inhibited by a single A/C mismatch in the DNA sequences. This result strongly suggests that the migration of holes, which are injected from the photoexcited TiO(2) into the DNA, through the DNA bases plays an important role in the photocatalytic cleavage of the conjugates. The influences of the photogenerated reactive oxygen species (ROS) on the cleavage efficiency were also examined. According to the experimental results, it was concluded that oxidation of the catechol moiety and/or the DNA damage are key reactions in this process.

Estimation of hydroxyl radical generation by salicylate hydroxylation method in multiple organs of mice exposed to whole-body X-ray irradiation.

Appropriate experimental conditions for the estimation of hydroxyl radical generation by salicylate hydroxylation were determined for multiple organs of X-irradiated mice in vivo. The in vitro experiments showed that there were significant correlations between the salicylic acid (SA) concentration, the amount of 2,3-dihydroxy benzoic acid (2,3-DHBA) and the X-ray exposure dose, and we obtained two linear-regression equations to calculate the amounts of hydroxyl radicals generated by the X-irradiation. The optimum dosage of SA and the appropriate sampling time for in vivo experiments was determined, and significant increases in the ratio of 2,3-DHBA to SA were detected in several organs of mice after X-irradiation. The hydroxyl radical equivalents of the 2,3-DHBA increases were also calculated. Our results clearly demonstrated the usefulness of the salicylate hydroxylation method in estimating hydroxyl radical generation in multiple organs in vivo.

Photosensitization by anticancer agents--10. ortho-semiquinone and superoxide radicals produced during anthrapyrazole-sensitized oxidation of catechols.

Photosensitized oxidation of catechol, 3,4-dihydroxybenzoic acid (DHBA), 3,4-dihydroxy-dihydrocinnamic acid (DHCA), and 3,4-dihydroxy-phenylalanine (DOPA) by novel anticancer agents, anthrapyrazoles (AP), has been studied employing EPR and the spin trapping technique. The formation of o-semiquinone radicals, the one-electron oxidation products of the catechols, stabilized in the form of zinc ion complexes, has been demonstrated. Rate constants for the disproportionation of the semiquinone radical/Zn2+ complexes in (DMSO)/acetate buffer (pH 4.5, 1:1 vol/vol; 100 mM Zn2+) mixture have been determined to be 0.35 x 10(4), 14 x 10(4), 8.8 x 10(4) and 3 x 10(4) M-1 s-1 for catechol, DHBA, DHCA and DOPA respectively. The presence of oxygen enhanced rather than inhibited the photogeneration of the o-semiquinone radicals and facilitated their EPR detection. The EPR spectrum of the superoxide radical adduct with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide was observed for the first time during photosensitized oxidation of the catechols in acidic aqueous solutions and in DMSO/acetate buffer mixture.