Kawabata Kohei, Kanoh Momoka, Okazaki Mayu, Maeda Rina, Mori Satomi, Akimoto Shiori, Inagaki Masanori, Nishi Hiroyuki
Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-ku, Hiroshima 731-0153, Japan.
Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Pharmaceuticals (Basel). 2020 Jun 26;13(6):135. doi: 10.3390/ph13060135.
It is important to develop a photostabilization strategy to ensure the quality of photosensitive compounds, including pharmaceuticals. This study focused on the protective effects of 20 amino acids on the photodegradation of naproxen (NX), a photosensitive pharmaceutical, to clarify the important nature of a good photostabilizer. Our previous report indicated the photodegradability of NX and the protective effects of some antioxidants on its photodegradation, therefore, this compound was used as a model compound. The degradation of NX in aqueous media during ultraviolet light (UV) irradiation and the protective effects of selected amino acids were monitored through high-performance liquid chromatography (HPLC), equipped with a reverse-phase column. Addition of cysteine, tryptophan, and tyrosine induced the significant suppression of NX photodegradation after UV irradiation for 3 h (residual amount of NX; 15.35%, 6.82%, and 15.64%, respectively). Evaluation of the antioxidative activity and UV absorption spectrum showed that cysteine suppressed NX degradation through its antioxidative ability, while tryptophan and tyrosine suppressed it through their UV filtering ability. Furthermore, three amino acids at higher concentrations (more than 100 µmol/L) showed more protective effects on NX photodegradation. For 10 mmol/L, residual amounts of NX with cysteine, tryptophan, and tyrosine were 58.51%, 69.34%, and 82.40%, respectively. These results showed the importance of both photoprotective potencies (antioxidative potency and UV filtering potency) and stability to UV irradiation for a good photostabilizer of photosensitive pharmaceuticals.
制定光稳定策略以确保包括药物在内的光敏化合物的质量非常重要。本研究聚焦于20种氨基酸对光敏药物萘普生（NX）光降解的保护作用，以阐明优质光稳定剂的重要特性。我们之前的报告指出了NX的光降解性以及一些抗氧化剂对其光降解的保护作用，因此，该化合物被用作模型化合物。通过配备反相柱的高效液相色谱（HPLC）监测紫外光（UV）照射期间水性介质中NX的降解以及所选氨基酸的保护作用。添加半胱氨酸、色氨酸和酪氨酸可在UV照射3小时后显著抑制NX的光降解（NX的残留量分别为15.35%、6.82%和15.64%）。抗氧化活性和UV吸收光谱评估表明，半胱氨酸通过其抗氧化能力抑制NX降解，而色氨酸和酪氨酸通过其UV过滤能力抑制NX降解。此外，三种氨基酸在较高浓度（超过100 μmol/L）时对NX光降解表现出更强的保护作用。对于10 mmol/L，半胱氨酸、色氨酸和酪氨酸存在时NX的残留量分别为58.51%、69.34%和82.40%。这些结果表明，对于光敏药物的优质光稳定剂而言，光保护能力（抗氧化能力和UV过滤能力）以及对UV照射的稳定性都很重要。
