Photochemical behavior of sitafloxacin, fluoroquinolone antibiotic, in an aqueous solution.
Sitafloxacin (STFX) hydrate, an antimicrobial agent, is photo-labile in aqueous solutions. The photodegradation rates (k) in neutral solutions were higher than those observed in acidic and alkaline solutions and maximum at the maximum absorption wavelength of STFX. The structures of photodegradation products were elucidated as 7-[7-amino-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid and 1-(1-amino-2-[16-fluoro-1-(2-fluoro-1-cyclopropyl)-1,4-dihydro-4-oxo-3-quinolin-7-yl]-amino]ethyl)cyclopropanecarbaldehyde. This implies that dechlorination is the key step in the photodegradation of STFX. The effect of halide ions on the photodegradation of STFX was estimated by observing the increments in the photostability of STFX with the addition of chloride ions. In contrast, in the presence of bromide ions, instead of increased photostability of the STFX rate, a new photodegradation product in the presence of bromide ion was observed. The structure of this new photodegradation product was an 8-bromo form of STFX, which was substituted for chlorine at the 8-position, so the dissociation of C-Cl bond at the 8-position of STFX was the rate-limiting step in the initial process of the photodegradation. STFX generated .C (carbon centered radical) and .OH (hydroxyl radical) in the process of photodegradation in a pH 4.0 buffer. On the contrary, STFX did not generate C in the presence of chloride ion in a pH 4.0 buffer. The .C was generated and then degraded into the above degradation products by photoirradiation in the absence of chloride ion, but the .C immediately reacted with chloride when it was present. As a result, the C-Cl bond was recovered leading to a possible increase in the apparent photostability.
Araki
Tetsuya
T
Chemical Technology Research Laboratories, Drug Metabolism and Physicochemical Properties Research Laboratory, Daiichi Pharmaceutical Co, Ltd, Tokyo, Japan. araki45s@daiichipharm.co.jp
Kawai
Yukinori
Y
Ohta
Ikumi
I
Kitaoka
Hiroaki
H
D000890:Anti-Infective Agents / Q000737:chemistry*; D001965:Bromides / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004355:Drug Stability; D024841:Fluoroquinolones; D006863:Hydrogen-Ion Concentration; D010782:Photolysis; D012996:Solutions
D000890:Anti-Infective Agents; D001965:Bromides; D002712:Chlorides; D024841:Fluoroquinolones; D012996:Solutions; C076246:sitafloxacin