PHOTODEGRADATION STUDIES OF 1,4-DIHYDROPYRIDINES BY MCR ANALYSIS ON UV SPECTRAL DATA

Photostability studies were performed on fifteen condensed 1,4-dihydropyridine (DHP) derivatives bearing cyclohexane ring with a bulky and lipophilic moiety (3-pyridylmethyl) in the ester group, recently synthesized. DHP molecules are well known to be highly sensitive to light. Photodegradation experiments were made according to the ICH rules, at 350 W/m2, corresponding to 21 kJ/min*m2. Degradation profiles were monitored by spectrophotometry and the data processed by multivariate curve resolution analysis to estimate the number of evolved components, their spectra and concentration profiles. The analysis of the spectral data showed a very different degradation rate for the DHP molecules, with the formation of a single photoproduct for two of them, furnishing the related oxidation product from aromatization of the pyridine ring. Traces of a second photoproduct were verified in twelve 1,4-DHPs and the formation of a third photoproduct only in one case. These stability results were compared with the activity values of each studied molecules, expressed as maximum relaxant response on smooth muscles and negative logarithm of the concentration giving the half-maximal response. 1,4-DHP molecules showed high stability when Fluorine atom (-F) was substituted in R1 position of the phenyl ring or when it was simultaneously present in both R1 and R2 position. In contrast, the chlorine substituent (-Cl) in R1 strongly increased the degradation. Chlorine (-Cl) or trifluoromethyl (-CF3) substituents in R2 position contributed to the stability of the molecules.