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.

译文

在这项研究中,在不同ph值的溶液中用UV/Vis光 (300-800 nm) 照射重要的H1抗组胺药物,即伊美斯汀 (EME) 、依平斯汀 (EPI) 和酮替芬 (KET)。接下来,通过新的高效液相色谱 (HPLC) 方法对它们进行分析,以估计降解百分比和相应的动力学。随后,使用超高效液相色谱串联质谱 (uplc-ms/MS) 鉴定其光降解产物并提出降解途径。此外,还检查了亚油酸的过氧化作用以及单线态氧 (SO) 和超氧阴离子 (SA) 的产生以及摩尔消光系数 (MEC) 的评估,以评估其光毒性风险。所有EME,EPI和KET的光降解均遵循伪一级动力学。在7.0和10.0的ph值下,EPI显示为相当稳定。然而,其在pH 3.0下的光稳定性较低。EME在整个ph值范围内均显示为光不稳定。反过来,KET显示在pH 3.0和7.0下适度不稳定。然而,它在pH 10.0的缓冲液中完全降解。结果,使用uplc-ms/MS方法分离并鉴定了几种光降解产物。最后,我们的ROS测定法按以下药物顺序显示出有效的光毒性风险: EPI < EME

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