Photostability studies on the furosemide-triamterene drug association.

The photostability of the diuretic drugs triamterene and furosemide, individually and combined, was evaluated. Spectrophotometric, spectrofluorimetric and chromatographic (HPLC) methods were applied to monitor the drug photodegradation. Furosemide was confirmed to be highly photolable in both pH 7.4 solution and methanol. Differently triamterene proved to be highly fluorescent (emission quantum yield: 0.9 in methanol and 0.8 in pH 7.4 solution), but essentially photostable (photochemical reaction quantum yield: congruent with 5 x 10(-4)) under exposure at 365 and 313 nm radiations. When the combined drugs in pH 7.4 solutions were exposed to 365 nm radiations a significant photoprotective effect of triamterene on furosemide was observed. The photoreactivity of the drugs was exploited to develop an HPLC method involving a post-column on-line photochemical derivatization useful to confirm the analyte identity in a commercial dosage form (tablets). The commercial product, containing the combined drugs, proved to be photostable also after long (65 h) light exposure.

Photoinduced covalent binding of frusemide and frusemide glucuronide to human serum albumin.

AIMS: To study reaction of photoactivated frusemide (F) and F glucuronide (Fgnd metabolite) with human serum albumin in order to find a clue to clarify a mechanism of phototoxic blisters from high frusemide dosage. METHODS: F was exposed to light in the presence of human serum albumin (HSA). HSA treated with this method (TR-HSA) was characterized by fluorescence spectroscopic experiment, alkali treatment and reversible binding experiment. RESULTS: Less 4-hydroxyl-N-furfuryl-5-sulphamoylanthranilic acid (4HFSA, a photodegradation product of F) was formed in the presence of HSA than in the absence of HSA. A new fluorescence spectrum excited at 320 nm was observed for TR-HSA. Alkali treatment of TR-HSA released 4HFSA. Quenching of the fluorescence due to the lone tryptophan near the warfarin-binding site of HSA was observed in TR-HSA. The reversible binding of F or naproxen to the warfarin-binding site of TR-HSA was less than to that of native HSA. These results indicate the photoactivated F was covalently bound to the warfarin-binding site of HSA. The covalent binding of Fgnd, which is also reversibly bound to the warfarin-binding site of HSA, was also induced by exposure to sunlight. Fgnd was more photoactive than F, indicating that F could be activated by glucuronidation to become a more photoactive compound. CONCLUSIONS: The reactivity of photoactivated F and Fgnd to HSA and/or to other endogenous compounds may cause the phototoxic blisters that result at high F dosage.

Photolytic degradation of frusemide.

Irradiation with 365 nm u.v. light of frusemide (4-chloro-N-furfuryl-5-sulphamoyl-anthranilic acid) in methanol results primarily in photoreduction to N-furfuryl-5-sulphamoylanthranilic acid and photohydrolysis to 4-chloro-5-sulphamoylanthranilic acid (saluamine).

Photosensitization by drugs: photolysis of some chlorine-containing drugs.

Irradiation with ultraviolet light of chlorpromazine, prochlorperazine, frusemide or hydrochlorothiazide in either aqueous or methanol solution yielded free chloride ion. Potentiometric methods were used to detect one mol of chloride ion produced per mol of drug irradiated in deoxygenated solution, with a concomitant equimolar appearance of hydrogen ion. Saturation of the solutions with oxygen strongly inhibited the photolysis reaction in methanol but only partially inhibited the production of Cl- and H+ in aqueous solution. The oxidation of 2,5-dimethylfuran is photosensitized by these drugs more effectively in methanol compared with aqueous solution. The photochemical behaviour is consistent with a photodissociative process occurring predominantly in methanol while photoionization predominates in aqueous media. No chloride ion was detected after extended irradiation of chlortetracycline, demeclocycline, chlordiazepoxide and hexachlorophane. The photolability of the chlorine in the compounds tested correlated with their ability to photosensitize oxidation by the Type I (free radical) mechanism.