The photolysis of Betamethasone (1), a synthetic glucocorticosteoid used for the treatment of rheumatic diseases and dermatologic disorders, has been studied both in organic and aqueous solution under UVA and UVB light. The drug decomposes up to 90 % under UVB light (18 J/cm2) and to 40 % under UVA light (30 J/cm2). Four main photoproducts have been isolated by TLC and characterized by NMR and MS analyses. They correspond to: 1a , the byciclo[3.1.0]hex-3-en-2-one rearranged derivative; 1b, the 1,11-oxysteroid derivative ; 1c, the 17-H derivative (formed by loss of 17 –OH) ; 1d, the 17 keto derivative, generated from a Norrish Type I reaction . Bethametasone also shows photosensitizing properties: it is able to induce photohemolysis under UVB (95 %, 1,5 J/cm2) and UVA light (55 %, 30 J/cm2). The isolated photoproducts also photohemolyze the RBC in the order of potency: 1c > 1a > 1b > 1d, thus proving to contribute to the overall photosensitizing properties of Betamethasone. The photostability of the drug was also studied in the solid state and in different pharmaceutical formulations. The presence of additives (such as sodium metabisulphite, phenol) have some photoprotective effect but they do not completely preserve the drug from photolysis. Therefore, both the loss of therapeutic activity and toxicity may be induced when Betamethasone is exposed to light.
Betamethasone: photolysis and phototoxicity
S. Caffieri;G. Miolo
2003
Abstract
The photolysis of Betamethasone (1), a synthetic glucocorticosteoid used for the treatment of rheumatic diseases and dermatologic disorders, has been studied both in organic and aqueous solution under UVA and UVB light. The drug decomposes up to 90 % under UVB light (18 J/cm2) and to 40 % under UVA light (30 J/cm2). Four main photoproducts have been isolated by TLC and characterized by NMR and MS analyses. They correspond to: 1a , the byciclo[3.1.0]hex-3-en-2-one rearranged derivative; 1b, the 1,11-oxysteroid derivative ; 1c, the 17-H derivative (formed by loss of 17 –OH) ; 1d, the 17 keto derivative, generated from a Norrish Type I reaction . Bethametasone also shows photosensitizing properties: it is able to induce photohemolysis under UVB (95 %, 1,5 J/cm2) and UVA light (55 %, 30 J/cm2). The isolated photoproducts also photohemolyze the RBC in the order of potency: 1c > 1a > 1b > 1d, thus proving to contribute to the overall photosensitizing properties of Betamethasone. The photostability of the drug was also studied in the solid state and in different pharmaceutical formulations. The presence of additives (such as sodium metabisulphite, phenol) have some photoprotective effect but they do not completely preserve the drug from photolysis. Therefore, both the loss of therapeutic activity and toxicity may be induced when Betamethasone is exposed to light.Pubblicazioni consigliate
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