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Analytical Studies on the Prediction of Photosensitive/Phototoxic Potential of Pharmaceutical Substances
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Research Paper
Analytical Studies on the Prediction of Photosensitive/Phototoxic Potential of Pharmaceutical Substances
Satomi Onoue1  and Yoshiko Tsuda1
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Analytical Research and Development, Pfizer Global Research and Development, Nagoya Laboratories, Pfizer Japan Inc., 5-2 Taketoyo, Aichi 470-2393, Japan |
Received: 27 May 2005 Accepted: 14 September 2005 Published online: 30 November 2006
Purpose Phototoxic responses after administration of photosensitive pharmaceutics have been recognized as undesirable side effects,
and predicting potential hazardous side effects is gaining importance as new drugs are introduced to the market. In this work,
we characterize the photochemical/photobiological properties of model compounds to develop an effective screening method for
the prediction of phototoxic/photosensitive potential.
Methods Twenty-one known photosensitive/phototoxic compounds and five weak/nonphototoxic compounds were subjected to ultraviolet (UV)
spectral analyses and photochemical evaluation including the determination of produced reactive oxygen species (ROS) and photostability
study. The photooxidation of linoleic acid was also monitored in the presence of tested compounds, guided on the formation
of thiobarbituric acid reactive substances.
Results Most photosensitive/phototoxic drugs tested, even weak UV absorbers, at a concentration of 200 μM showed significant production
of ROS under 18 h light exposure (30,000 lx). On the other hand, ROS generated from weak/nonphototoxic compounds, including
strong UV absorber benzocaine, were low or negligible. Although exposure of quinine to light resulted in significant degradation
(half-life, t1/2 = 6.4 h), it was dramatically attenuated by the addition of ROS scavengers, especially sodium azide ( t1/2 = 122.6 h). Furthermore, concomitant exposure of photosensitive/phototoxic compounds (200 μM) and linoleic acid (1 mM) for
18 h led to the marked formation of lipoperoxide.
Conclusion Results indicated that known photosensitive/phototoxic compounds tested have the ability to generate ROS under light exposure,
and this photochemical reaction could be associated with their photoinstability and/or phototoxic responses. Based on these
findings, determination of ROS, generated from photoirradiated compounds, may be an effective predictive model in recognizing
their photosensitive/phototoxic potential.
Key Words lipid peroxidation - phototoxicity - reactive oxygen species - singlet oxygen - superoxide
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