Photodegradation of the H<sub>1</sub> Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity
In this study, important H<sub>1</sub> 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) me...
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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/6/560 |
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| author | Anna Gumieniczek Anna Berecka-Rycerz Urszula Hubicka Paweł Żmudzki Karolina Lejwoda Paweł Kozyra |
| author_facet | Anna Gumieniczek Anna Berecka-Rycerz Urszula Hubicka Paweł Żmudzki Karolina Lejwoda Paweł Kozyra |
| author_sort | Anna Gumieniczek |
| collection | DOAJ |
| description | In this study, important H<sub>1</sub> 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. |
| first_indexed | 2024-03-10T19:06:46Z |
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| id | doaj.art-1a396a7052dd4e66aab5d78c5b25db20 |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T19:06:46Z |
| publishDate | 2020-06-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-1a396a7052dd4e66aab5d78c5b25db202023-11-20T04:05:47ZengMDPI AGPharmaceutics1999-49232020-06-0112656010.3390/pharmaceutics12060560Photodegradation of the H<sub>1</sub> Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent PhototoxicityAnna Gumieniczek0Anna Berecka-Rycerz1Urszula Hubicka2Paweł Żmudzki3Karolina Lejwoda4Paweł Kozyra5Department of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, PolandDepartment of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, PolandDepartment of Inorganic and Analytical Chemistry, Jagiellonian University, Collegium Medicum, Medyczna 9, 30-688 Cracow, PolandDepartment of Medicinal Chemistry, Jagiellonian University, Collegium Medicum, Medyczna 9, 30-688 Cracow, PolandDepartment of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, PolandDepartment of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, PolandIn this study, important H<sub>1</sub> 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.https://www.mdpi.com/1999-4923/12/6/560H<sub>1</sub> antihistaminicstopical formulationsphotodegradation kineticsphotodegradation pathwaysphototoxicityreactive oxygen species |
| spellingShingle | Anna Gumieniczek Anna Berecka-Rycerz Urszula Hubicka Paweł Żmudzki Karolina Lejwoda Paweł Kozyra Photodegradation of the H<sub>1</sub> Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity Pharmaceutics H<sub>1</sub> antihistaminics topical formulations photodegradation kinetics photodegradation pathways phototoxicity reactive oxygen species |
| title | Photodegradation of the H<sub>1</sub> Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity |
| title_full | Photodegradation of the H<sub>1</sub> Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity |
| title_fullStr | Photodegradation of the H<sub>1</sub> Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity |
| title_full_unstemmed | Photodegradation of the H<sub>1</sub> Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity |
| title_short | Photodegradation of the H<sub>1</sub> Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity |
| title_sort | photodegradation of the h sub 1 sub antihistaminic topical drugs emedastine epinastine and ketotifen and ros tests for estimations of their potent phototoxicity |
| topic | H<sub>1</sub> antihistaminics topical formulations photodegradation kinetics photodegradation pathways phototoxicity reactive oxygen species |
| url | https://www.mdpi.com/1999-4923/12/6/560 |
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