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Article

Photodegradation of the H1 Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity

1
Department of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland
2
Department of Inorganic and Analytical Chemistry, Jagiellonian University, Collegium Medicum, Medyczna 9, 30-688 Cracow, Poland
3
Department of Medicinal Chemistry, Jagiellonian University, Collegium Medicum, Medyczna 9, 30-688 Cracow, Poland
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(6), 560; https://doi.org/10.3390/pharmaceutics12060560
Received: 27 May 2020 / Revised: 11 June 2020 / Accepted: 15 June 2020 / Published: 17 June 2020
(This article belongs to the Special Issue Formulation of Photosensitive Drugs)
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. View Full-Text
Keywords: H1 antihistaminics; topical formulations; photodegradation kinetics; photodegradation pathways; phototoxicity; reactive oxygen species H1 antihistaminics; topical formulations; photodegradation kinetics; photodegradation pathways; phototoxicity; reactive oxygen species
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MDPI and ACS Style

Gumieniczek, A.; Berecka-Rycerz, A.; Hubicka, U.; Żmudzki, P.; Lejwoda, K.; Kozyra, P. Photodegradation of the H1 Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity. Pharmaceutics 2020, 12, 560. https://doi.org/10.3390/pharmaceutics12060560

AMA Style

Gumieniczek A, Berecka-Rycerz A, Hubicka U, Żmudzki P, Lejwoda K, Kozyra P. Photodegradation of the H1 Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity. Pharmaceutics. 2020; 12(6):560. https://doi.org/10.3390/pharmaceutics12060560

Chicago/Turabian Style

Gumieniczek, Anna, Anna Berecka-Rycerz, Urszula Hubicka, Paweł Żmudzki, Karolina Lejwoda, and Paweł Kozyra. 2020. "Photodegradation of the H1 Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity" Pharmaceutics 12, no. 6: 560. https://doi.org/10.3390/pharmaceutics12060560

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