Kawabata Kohei, Muraoka Haruka, Miyara Masatsugu, Kotake Yaichiro, 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, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8553, Japan.
Anal Sci. 2023 Nov;39(11):1791-1803. doi: 10.1007/s44211-023-00400-x. Epub 2023 Aug 4.
Nitrendipine (NTR) is a dihydropyridine drug, which is well-known as a photodegradable pharmaceutical. However, the photochemical reaction of NTR has not been evaluated in detail from now. In this study, we perform the photodegradation profiling of NTR for the elucidation of its photochemical behavior. NTR amounts during ultraviolet light (UV) irradiation were monitored using high performance liquid chromatography (HPLC). NTR was photodegraded almost completely within 24 h along with the generation of some photoproducts. Structural determination of two NTR photoproducts were carried out by means of electrospray ionization liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). Obtained results from this study clarified one novel NTR photoproduct, a nitroso pyridine analogue, in addition to a pyridine analogue. Furthermore, photodegradation pathway of NTR was speculated based on chemical structures of NTR photoproducts to clarify its photochemical behavior. It was proposed that a singlet oxygen molecule might withdraw two hydrogen radicals resulting in the form of a pyridine analogue, and the following reduction of its nitro group might produce a nitroso pyridine analogue. Finally, we evaluated the photostability of NTR tablets and its altered forms, indicating that the change of the dosage form led to a decrease of the photostability of NTR tablets. The obtained results will be helpful for the additional research to evaluate the effect of NTR photodegradation on its own biological activities.
尼群地平（NTR）是一种二氢吡啶类药物，是一种众所周知的可光降解药物。然而，到目前为止，NTR的光化学反应尚未得到详细评估。在本研究中，我们对NTR进行了光降解分析，以阐明其光化学行为。使用高效液相色谱法（HPLC）监测紫外线（UV）照射过程中的NTR含量。NTR在24小时内几乎完全光降解，并生成了一些光产物。通过电喷雾电离液相色谱串联质谱法（LC-ESI-MS/MS）对两种NTR光产物进行了结构测定。本研究获得的结果表明，除了一种吡啶类似物外，还发现了一种新型的NTR光产物，即亚硝基吡啶类似物。此外，根据NTR光产物的化学结构推测了NTR的光降解途径，以阐明其光化学行为。有人提出，单线态氧分子可能夺取两个氢自由基，形成吡啶类似物，随后其硝基的还原可能产生亚硝基吡啶类似物。最后，我们评估了NTR片剂及其改变形式的光稳定性，结果表明剂型的改变导致NTR片剂的光稳定性降低。所得结果将有助于进一步研究评估NTR光降解对其自身生物活性的影响。
