Photosensitization by Norfloxacin is a Function of pH

Abstract

Norfloxacin is a fluoroquinolone (FQ) antibiotic that has been reported to cause cutaneous photosensitivity in animals and occasionally in humans. We have studied the fluorescence and singlet oxygen (1O2)-generating properties of norfloxacin. Upon UV excitation the drug fluoresces in water, and the relative intensities of two major fluorescence bands at ca 420 and 450 nm are affected by pH. The overall quantum yield of fluorescence (phi F) is also strongly pH dependent: phi F is low in 0.2 N HCl solution (0.2), increasing steeply to 0.12 at pH 4, then gradually decreasing to 0.01 at pH 10. The changes in phi F are accompanied by changes in fluorescence lifetime from 0.6 ns at pH 1 to 1.8 ns at pH 4. Norfloxacin exhibits phosphorescence in low temperature glasses. The formation of a triplet state at room temperature is also suggested by 1O2 phosphorescence in aerobic D2O. This phosphorescence is "self-quenched" by norfloxacin itself with an efficiency that is pH dependent: kq is 7.9 x 10(6) M-1 s-1 at pD 4, decreases to 1.9 x 10(6) M-1 s-1 at pD 7.5 but then increases about 20-fold in alkaline D2O solutions. This quenching causes the observed 1O2 production by norfloxacin (0.1 mM) to show a maximum at around pH 8-9. However, after correction for self-quenching, the quantum yield of 1O2 production (phi 50)y measured by using perinaphthenone as a standard, yielded the following values: phi s0 is about 0.07 in 0.2 N DCI solution, 0.08 at pH 7.5 and then increases smoothly to approximately 0.2 in 0.1 M NaOD solution. The relatively high, unquenched 1O2 production at physiological pH 7.4 (phi s0 approximately 0.08) suggests that 1O2 reactions may play an important role in the cutaneous phototoxicity of norfloxacin and other FQ antibiotics.

Enhanced Photostability of Fluoroquinolone Antibacterials Capped on Silver Nanoparticles

“…form (see Scheme 1 for clarity) is not fluorescent whereas both the zwitterionic and cationic forms strongly emit with maxima peaked at well-different wavelengths. [21,23,33] As reported in Figure 3, the free NF and RF show intense fluorescence emission arising from their zwitterionic forms with maxima at 430 and 470 nm, respectively, according to literature (spectra a in Figure 3). These emissions were slightly red-shifted in the case of Ag@FQs confirming that the fluorescence observed originates from the zwitterionic FQs bound to the AgNPs.…”

“…Photodegradation of many FQs is also strongly dependent on pH. [19][20][21] In particular, the zwitterionic form, which dominates at physiological pH, is the most photolabile representing a serious drawback for the use in therapy. The picture emerging from these considerations suggests a critical need in finding suitable systems that may improve the drug photostability.…”

“…[21,23,33] Therefore, fluorescence spectroscopy represents a powerful diagnostic tool to get more insights into binding nature with the metal nanoparticles. In particular, the anionic S. Giuffrida and S. Sortino/Enhanced Photostability of Fluoroquinolone Antibacterials .…”

Pulse radiolysis study on several fluoroquinolones

“…Apart from this reaction, other photochemical properties of FQs, such as decarboxylation, side-chain degradation, the effect of medium, and pH dependence of FQ excited states were also investigated by photochemists, and have also been reported in detail (Albini and Monti, 2003;Bilski et al, 1996;Bilski et al, 1998;Fasani et al, 1998;Sortino et al, 1998;Fasani et al, 1999a,b;Sortino et al, 1999;Bazin et al, 2000;Park et al, 2000;Sortino et al, 2000;Fasani et al, 2001;Monti and Sortino 2002;Park et al, 2002a,b;Viola et al, 2004;Lorenzo et al, 2008a,b;Lorenzo et al, 2009;Ge et al, 2010).…”

The dynamics of a novel method coupling high‐performance liquid chromatography with resonance Rayleigh scattering

“…The UV and fluorescence spectra characteristic of FQs were strongly affected by the pH, acetonitrile and other aprotic solvents [16][17][18]. Owing to the complex environmental matrix, one reason for FQs residues is the lack of reliable and effective analytical methods.…”