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Standardized UV-vis spectra as the foundation for a threshold-based, integrated photosafety evaluation

Bauer, Daniel and Averett, Lacey A and De Smedt, Ann and Kleinman, Mark H and Muster, Wolfgang and Pettersen, Betty A and Robles, Catherine (2014) Standardized UV-vis spectra as the foundation for a threshold-based, integrated photosafety evaluation. Regulatory Toxicology and Pharmacology, 68 (1). pp. 70-75. ISSN 02732300

Abstract

Phototoxicity is a relatively common phenomenon and is an adverse effect of some systemic drugs. The fundamental initial step of photochemical reactivity is absorption of a photon; however, little guidance has been provided thus far regarding how ultraviolet–visible (UV–vis) light absorption spectra may be used to inform testing strategies for investigational drugs. Here we report the results of an inter-laboratory study comparing the data from harmonized UV–vis light absorption spectra obtained in methanol with data from the in vitro 3T3 Neutral Red Uptake Phototoxicity Test. Six pharmaceutical companies submitted data according to predefined quality criteria for 76 compounds covering a wide range of chemical classes showing a diverse but ‘‘positive’’-enhanced distribution of photo irritation factors (22%: PIF < 2, 12%: PIF 2–5, 66%: PIF > 5). For compounds being formally positive (PIF value above 5) the lowest reported molar extinction coefficient (MEC) was 1700 L mol�1 cm�1 in methanol. However, the majority of these formally positive compounds showed MEC values being significantly higher (up to almost 40,000 L mol�1 cm�1). In conclusion, an MEC value of 1000 L mol�1 cm�1 may represent a reasonable and pragmatic threshold warranting further experimental photosafety evaluation.

Item Type: Article
Keywords: Photosafety , phototoxicity, photoreactivity, molar extinction coefficient, molar absorptivity, threshold, sun light, irradiation
Date Deposited: 26 Apr 2016 23:46
Last Modified: 26 Apr 2016 23:46
URI: https://oak.novartis.com/id/eprint/10871

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