Photodegradation of amiloride in aqueous solution

The photodegradation of amiloride hydrochloride in deaerated aqueous solution at 30 degrees C in the pH range 4.5-11.0 was studied by spectrophotometry and reversed-phase HPLC. The neutral form of the drug present in alkaline solution degraded approximately 3-fold faster than the cationic form. The quantum yields for photodegradation of neutral amiloride and its conjugate acid were determined using ferrioxalate actinometry to be 0.023 +/- 0.002 and 0.009 +/- 0.001, respectively. The initial photoreaction involves dechlorination of amiloride and the major product is N-amidino-3,5-diamino-6-hydroxylpyrazine-carboxamide, established by UV, H-1 and C-13 NMR, and chemical ionization-mass spectrometry. The mechanism of photolysis is postulated to involve cation radical formation that facilitates the dechlorination step. The photosensitizing activity of amiloride hydrochloride was tested by measuring (a) the rate of oxygen uptake in the presence of singlet oxygen substrates, 2,5-dimethylfuran or L-histidine, and (b) the rate of free radical polymerization of acrylamide, at 30 degrees C in aqueous solution. Photosensitization by amiloride was concluded to occur predominantly via singlet oxygen rather than a free radical mechanism. However, amiloride is a much weaker photosensitizer than other diuretics such as frusemide and hydrochlorothiazide, tested under the same experimental conditions. (C) 1999 Elsevier Science B.V. All rights reserved.