| Summary: | 碩士 === 國立中正大學 === 化學暨生物化學研究所 === 101 === This study used high performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS) to analyze the interactions between dihydropyridine (1,4-DHP) drug after photodegradation and vitamin C (VitC), and to purify and characterize the after formed new compounds.
In the first part, a study on a calcium channel blocker Nifedipine (NF), currently used as an antihypertensive drug, is conducted. This photo-sensitive drug undergoes conformational changes and may even become photo-toxic after UV light and sunlight exposure. In terms of photodegradation products, only limited studies indicated that NF under light exposure would transform into -nitro (-NO2) or -nitroso (-NO) derivatives. Considering the some 1,4-DHP drug is very photo-sensitive, if patients with hypertension took this medication without protection from light exposure will lead an interaction between photodegraded 1,4-DHP and VitC in human serum and liver tissues. Therefore, the first part of the study aimed to investigate the interactions between VitC and 1,4-DHP antihypertensive drug under light or UV exposure. We found that during photodegradation of NF, a specific reaction with VitC occurred and was most prominent changes at 280 and 310 nm wavelengths of UV-Vis spectrum were observed. The results of control group revealed that the spectral changes originated in precence of VitC. This unknown reaction could come from a compound photosynthesized by NF and VitC, or a brand new synthesis, which is very valuable for farther chemical and pharmaceutical research. Hence we will analyze this new reaction and ascertain its chemical mechanism, as well as purity and identify the newly synthesized compound.
In the second part, we investigated the possibility of proceeding the interaction to VitC by replacing another photosensitive 1,4-DHP medicine, Nisoldipine (NS), with an ortho-nitro (-NO2) base. An analog, Nimodipine (NM), a 1,4-DHP with meta-nitro (-NO2) group, was used as a control. Moreover, for safety concerns, an examination on the changes of activity levels of the new compound to other calcium channel blockers will be performed. Since the effects of NF on atherosclerosis were known, it is also valuable to see the influences of the new compounds on atherosclerosis. These new compounds may become a potential new medicine with effectiveness on hypertension or atherosclerosis.
Keywords: nifedipine, nisoldipine, nimodipine, 1,4-DHP, vitamin C, ESI-MS, UV-Vis
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