Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
AAPS PharmSciTech. 2018 Apr;19(3):1182-1190. doi: 10.1208/s12249-017-0929-4. Epub 2017 Dec 18.
The photodegradation study is essential for the phototoxicity assessment of fluoroquinolones. Various LC-MS techniques and ultraviolet (UV) lamp irradiation conditions have been used for the identification of their photodegradation products. In this study, visible light (400-760 nm) lamp irradiation was selected for the photodegradation of moxifloxacin (MOXI) hydrochloride solutions. Two photodegradation products were identified by LC-MS/MS at first, but one product could not be speculated from the mass spectrum and any known degradation mechanisms. To obtain an adequate amount for the structure elucidation, this unknown product was isolated by recrystallization and semi-preparative HPLC. Then, its structure was further identified by H-NMR, C-NMR, and 2D-NMR. Based on spectral data, this new photodegradation product was unambiguously named as 7-[3-(3-aminopropyl)-1H-pyrrol-1-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which was formed through the open of hexahydroxy N-containing heterocycle and the formation of two alkene bonds in pyrrole ring. The effects of solution pH value on the formation of photodegradation products were compared. Their production was minimum at pH 5.0 and maximum at pH 7.0. Because MOXI hydrochloride has been used extensively in clinical practice and visible light is the most possible light source that pharmaceutical products are exposed to, our study is important for the quality control of MOXI liquid preparations.
光降解研究对于氟喹诺酮类药物的光毒性评估至关重要。已经使用了各种 LC-MS 技术和紫外线 (UV) 灯照射条件来鉴定它们的光降解产物。在这项研究中，选择可见光（400-760nm）灯照射来进行盐酸莫西沙星（MOXI）溶液的光降解。首先通过 LC-MS/MS 鉴定了两种光降解产物，但有一种产物无法从质谱和任何已知的降解机制中推断出来。为了获得足够的量进行结构阐明，通过重结晶和半制备 HPLC 分离出这种未知产物。然后，通过 1H-NMR、13C-NMR 和 2D-NMR 进一步确定其结构。根据光谱数据，这个新的光降解产物被明确命名为 7-[3-(3-氨丙基)-1H-吡咯-1-基]-1-环丙基-6-氟-8-甲氧基-4-氧代-1,4-二氢喹啉-3-羧酸，它是通过六元含氮杂环的开环和吡咯环中两个烯键的形成而形成的。比较了溶液 pH 值对光降解产物形成的影响。在 pH 值为 5.0 时，产物生成最少，在 pH 值为 7.0 时，产物生成最多。由于盐酸莫西沙星在临床实践中被广泛应用，并且可见光可能是药物产品暴露的最常见光源，因此我们的研究对于 MOXI 液体制剂的质量控制非常重要。
