Abstract
In this study, important H1 antihistaminic drugs, i.e., emedastine (EME), epinastine (EPI), and ketotifen (KET), were irradiated with UV/Vis light (300–800 nm) in solutions of different pH values. Next, they were analyzed by new high performance liquid chromatography (HPLC) methods, in order to estimate the percentage of degradation and respective kinetics. Subsequently, ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) was used to identify their photodegradation products and to propose degradation pathways. In addition, the peroxidation of linoleic acid and generation of singlet oxygen (SO) and superoxide anion (SA) were examined, together with the molar extinction coefficient (MEC) evaluation, to estimate their phototoxic risk. The photodegradation of all EME, EPI, and KET followed pseudo first-order kinetics. At pH values of 7.0 and 10.0, EPI was shown to be rather stable. However, its photostability was lower at pH 3.0. EME was shown to be photolabile in the whole range of pH values. In turn, KET was shown to be moderately labile at pH 3.0 and 7.0. However, it degraded completely in the buffer of pH 10.0. As a result, several photodegradation products were separated and identified using the UPLC-MS/MS method. Finally, our ROS assays showed a potent phototoxic risk in the following drug order: EPI < EME < KET. All of these results may be helpful for manufacturing, storing, and applying these substantial drugs, especially in their ocular formulations.
Highlights
The sensitivity of an active pharmaceutical substance (API) to light may vary with its chemical structure and reactivity, as well as the proposed dosage forms
As the primary event of a phototoxic reaction, the substance is excited by the absorption of photon energy, and the photoexcited chemical can react with other substances through energy transfer and/or radical reactions, possibly leading to phototoxicity [3,22]
A UV/Vis spectral analysis is recommended by the official guidelines as the first step of photosafety testing in the pharmaceutical industry [24]
Summary
The sensitivity of an active pharmaceutical substance (API) to light may vary with its chemical structure and reactivity, as well as the proposed dosage forms. For many APIs and formulations, photoreactivity leads to chemical degradation or to changes in their physical appearance [1,2]. Many classes of drugs have the potential to provoke phototoxic, photoallergic, and photogenotoxic effects in tissues exposed to light [1,3]. Pharmaceutics 2020, 12, x FOR PEER REVIEW. Emedastine (EME), epinastine (EPI), and ketotifene (KET) belong to H1 histaminic receptor antagonists, exhibiting varied activity and several specific properties. EME is known as a competitive of theasHwell
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
