Comparison of photosensitivity of five dihydropyridines

OBJECTIVES: To compare the photosensitivity of five 1, 4- dihydropyridines (1, 4-DHPs) to sunlight, diffused light and tungsten lamp and study the quantitative structure-activity relationship of five 1, 4-DHPs between the photosensitivity and 4-substituents and 4-substituented phenyl group. METHODS: Five 1, 4-DHPs were exposed to sunlight, diffused light and tungsten lamp respectively. Samples taken at different time were analyzed by reversed-phase high performance liquid chromatography. Photochemical degradation rate constant (K(app)) and half-time (t( 1/4 )) of each 1, 4-DHPs were determined. The QSAR of five 1, 4-DHPs between the V(x) and 4- substituents and K(app) and t( 1/4 ) was worked out respectively. RESULTS: Nifedipine was photochemically degraded in first order reaction when exposed to sunlight, diffused light and tungsten lamp, and the K(app) was (1.02 ± 0.20)min^-1, (0. 022 ± 0. 006)min^-1 and (0. 015 ± 0. 004) min^-1, respectively. m-nifedipine, furandipine, chlorophenyldipine and phenyldipine were photochemically stable when exposed to diffused light and tungsten lamp. However, they were photochemically degradable when exposed to direct sunlight and the K(app) of them was (0.21 ± 0.07)h^-1, (0.03 ± 0.02)h^-1, (0.019 ± 0.003)h^-1 and (0.012 ± 0.001)h^-1, respectively. The t( 1/4 ) of five 1, 4-DHPs when exposed to sunlight was 0.68 min, 3.3, 24, 37 and 58 h, respectively. QSAR equation: K(app)= 2.008 1 - 2.987 6 V(x) + 1. 088 5(V(x))² - 2.574 9 x 10^-5(V(x))³(r = 0. 904 6). CONCLUSION: The photosensitivity of 1, 4-DHPs are related not only to 4-substituents, but also to the properties and positions of the substituents on 4-phenyl group.