Radiosterilization of drugs in aqueous solutions may be achieved by the use of radioprotective excipients.

The aim of this study was to assess the feasibility of radiosterilization of drugs aqueous solutions and to evaluate the effects of some additives, such as mannitol, nicotinamide and pyridoxine, which might protect the drug from degradation. Metoclopramide was selected as a model drug. The structures of the degradation products were determined to gain insight on the radiolysis mechanisms in aqueous solution in order to design strategies to lower the drug degradation. Metoclopramide hydrochloride aqueous solutions with and without excipients were irradiated either with gamma rays or high-energy electrons. HPLC-DAD was used to measure the loss of chemical potency and to quantify the degradation products which were also characterized by LC-APCI-MS-MS. Metoclopramide recovery for gamma and electron beam-irradiated solutions containing either mannitol, pyridoxine or nicotinamide meets the pharmacopoeial specifications for metoclopramide content up to a 15 kGy irradiation so that metoclopramide solutions containing these excipients might be radiosterilized at 15 kGy either with gamma rays or high-energy electrons. Structures are proposed for the majority of radiolysis products. Similar radiolysis products were detected for gamma and electron beam irradiations but the chromatographic profiles were different (differences in the distribution of radiolysis products).

Light-dependent generation of reactive oxygen species in cell culture media.

Cell culture media (RPMI 1640, Dulbecco's Minimal Essential Medium and yeast extract-peptone-glucose medium) were found to oxidize dichlorodihydrofluorescein diacetate and dihydrorhodamine 123, and to generate spin adduct of 5,5'-dimethyl-1-pyrroline N-oxide, which indicates formation of reactive oxygen species (ROS). The production of ROS was light dependent. The main component of the media responsible for the generation of ROS was riboflavin, but tryptophan, tyrosine, pyridoxine, and folic acid enhanced the effect of riboflavin. These observations point to exposure of cells to ROS under in vitro culture conditions.

Avaliaçäo dos efeitos da radiaçäo ionizante de 'POT. 60 Co' em propriedades físicas, químicas e nutricionais dos feijöes Phaseolus vulgaris L. e Vigna unguiculata (L.) Walp / Evaluation of he effects of 'POT. 60 Co' in nutritional, chemical and physicas properties of beans Phaseolus vulgaris L and Vigna unguiculata (L.) Walp

Foram estudados os efeitos da radiaçäo ionizante de 'POT. 60 Co' nas doses de 0; 0,5; 1,0; 2,5; 5,0 e 10 kGy e do período de estocagem de 6 meses nos feijöes, Phaseolus vulgaris L., variedade carioca e Vigna unguiculata (L.) Walp, variedade macaçar. Determinou-se o tempo de cocçäo, seguido das análises: sensorial, vitaminas B1, B2 e B6, quantidade protéica, avaliaçäo biológica em ratos [Consumo Alimentar (CA) e Ganho de Peso (GP) em gramas, Digestibilidade aparente (NPUa) e Valor Biológico aparente (VBa)] e a aplicabilidade de métodos de detecçäo de alimentos irradiados com testes de germinaçäo, análise da migraçäo do DNA, termoluminescência e análise dos hidrocarbonetos formados pela radiaçäo. Mudanças no tempo de cocçäo foram observadas em todas as doses. Quando aplicadas doses até 1 kGy, näo houve modificaçäo das qualidades nutricionais dos feijöes processados por radiaçäo. A aplicaçäo dos métodos de detecçäo de alimentos irradiados propostos, possibilitaram a detecçäo dos feijöes irradiados com doses baixas de até 0,5 kGy

Pyridoxine toxicity to cultured fibroblasts caused by near-ultraviolet light.

Pyridoxine, like riboflavin, has absorption in the range of near ultraviolet (UVA; 320-400 nm) radiation and is known to decompose after long irradiation with germicidal lamps. Thus, the possibility of UVA-induced pyridoxine photosensitization was studied in cultured normal human, hydroa vacciniforme, and xeroderma pigmentosum fibroblasts. Cytotoxicity caused by the sensitization was measured by post-UVA colony formation. Pyridoxine showed strong cytotoxic effect after UVA radiation and the effect remained for at least 60 min after UVA radiation. Although the cytotoxicity decreased a little when pyridoxine was irradiated under anaerobic conditions, the amount of hydrogen peroxide produced by UVA radiation was hardly cytotoxic and the rate of photodecomposition of pyridoxine was slower under anaerobic conditions than aerobic ones. Thus, the toxicity seemed to depend mostly on the photoproducts of pyridoxine. The UVA-induced pyridoxine cytotoxicity was not due to DNA damage that is to be excision-repaired because group A and C xeroderma pigmentosum fibroblasts were killed as in the case of normal human fibroblasts.

Effect of dyes on the photodecomposition of pyridoxine and pyridoxamine.

Erythrosine, eosine Y, rose bengal, mercurochrome, methylene blue, azure A and azure B accelerated the photodecomposition of pyridoxine and pyridoxamine at pH 5-9, but fluorescein and acid red did not. The photodecomposition of pyridoxine in the presence of erythrosine was greatest at pH 9.0. The singlet oxygen generated by light-excited dyes played a role as a mediator in the decomposition of pyridoxine and pyridoxamine in the presence of dyes was depressed by aminopyrine, sulpyrine and tryptophan. Pyridoxine 3,4'-dioctanoate was stable in the presence of erythrosine.

Stability of three forms of vitamin B6 to laboratory light conditions.

Pyridoxine.HCl, pyridoxal.HCl, and pyridoxamine.2HCl solutions were exposed to several laboratory light treatments, and the resulting vitamin retentions were determined by the AOAC microbiological method. The 5 treatments compared were total darkness, regular laboratory light, low actinic glass protection, yellow incandescent light, and golden fluorescent light. All treatments were imposed for 8 and 15 hr, and with the vitamin solutions at both a low and a high pH. Regular laboratory light was the most destructive to the vitamins, with greater destruction at higher pH and longer exposure time in all cases. Pyridoxine retentions ranged from 97 (pH 4.5, 8 hr) to 66% (pH 7, 15 hr); pyridoxal from 97 (pH 4.5, 8 hr) to 55% (pH 6, 15 hr); and pyridoxamine from 81 (pH 4.5, 8 hr) to 47% (pH 8, 15 hr). Retentions in low actinic glassware or in clear glassware under yellow or golden fluorescent light were essentially com,lete, ranging from 94 to 106% over all treatments and all 3 forms. Results showed that either of the 2 subdued light conditions, yellow or golden fluorescent light, is suitable in vitamin B6 assays and that low actinic glassware is suitable for storing sample solutions.